RapamycinFungusV1, Main, Exploration, bibRecord, 000751

Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.

Identifieur interne : 000751 ( Main/Exploration ); précédent : 000750; suivant : 000752

Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.

Source :

PLoS biology [ 1545-7885 ] ; 2017.

RBID : pubmed:28821013

Descripteurs français

English descriptors

KwdEn :
- Actins (metabolism), Agammaglobulinaemia Tyrosine Kinase (MeSH), Animals (MeSH), B-Lymphocytes (metabolism), Bridged Bicyclo Compounds, Heterocyclic (MeSH), Carrier Proteins (metabolism), Cell Membrane (metabolism), Cytoskeletal Proteins (metabolism), Immunity, Humoral (MeSH), Male (MeSH), Mice, Inbred C57BL (MeSH), Mice, Knockout (MeSH), Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases (metabolism), Polymerization (MeSH), Protein-Tyrosine Kinases (metabolism), Rapamycin-Insensitive Companion of mTOR Protein (MeSH), Thiazolidines (MeSH).
MESH :
- chemical , metabolism : Actins, Carrier Proteins, Cytoskeletal Proteins, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases, Protein-Tyrosine Kinases.
- chemical : Agammaglobulinaemia Tyrosine Kinase, Bridged Bicyclo Compounds, Heterocyclic, Rapamycin-Insensitive Companion of mTOR Protein, Thiazolidines.
- metabolism : B-Lymphocytes, Cell Membrane.
- Animals, Immunity, Humoral, Male, Mice, Inbred C57BL, Mice, Knockout, Polymerization.

Abstract

As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling. We found that the key positive and negative BCR signaling molecules, phosphorylated Brutons tyrosine kinase (pBtk) and phosphorylated SH2-containing inositol phosphatase (pSHIP), are reduced and enhanced, respectively, in Rictor KO B cells. This suggests that Rictor positively regulates the early events of BCR signaling. We found that the cellular filamentous actin (F-actin) is drastically increased in Rictor KO B cells after BCR stimulation through dysregulating the dephosphorylation of ezrin. The high actin-ezrin intensity area restricts the lateral movement of BCRs upon stimulation, consequently reducing BCR clustering and BCR signaling. The reduction in the initiation of BCR signaling caused by actin alteration is associated with a decreased humoral immune response in Rictor KO mice. The inhibition of actin polymerization with latrunculin in Rictor KO B cells rescues the defects of BCR signaling and B cell differentiation. Overall, our study provides a new pathway linking cell metablism to BCR activation, in which Rictor regulates BCR signaling via actin reorganization.

DOI: 10.1371/journal.pbio.2001750
PubMed: 28821013
PubMed Central: PMC5562439

Affiliations:

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Le document en format XML

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<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
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<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
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<author><name sortKey="Li, Qubei" sort="Li, Qubei" uniqKey="Li Q" first="Qubei" last="Li">Qubei Li</name>
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<author><name sortKey="Shi, Chunwei" sort="Shi, Chunwei" uniqKey="Shi C" first="Chunwei" last="Shi">Chunwei Shi</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
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</placeName>
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</author>
<author><name sortKey="Yu, Bing" sort="Yu, Bing" uniqKey="Yu B" first="Bing" last="Yu">Bing Yu</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
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<author><name sortKey="Miller, Heather" sort="Miller, Heather" uniqKey="Miller H" first="Heather" last="Miller">Heather Miller</name>
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<wicri:regionArea>Department of Intracellular Pathogens, National Institute of Allergy and Infectious Diseases, Hamilton, Montana</wicri:regionArea>
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</placeName>
</affiliation>
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<author><name sortKey="Yang, Gangyi" sort="Yang, Gangyi" uniqKey="Yang G" first="Gangyi" last="Yang">Gangyi Yang</name>
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<wicri:regionArea>Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Westerberg, Lisa S" sort="Westerberg, Lisa S" uniqKey="Westerberg L" first="Lisa S" last="Westerberg">Lisa S. Westerberg</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea>
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</placeName>
</affiliation>
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<author><name sortKey="Liu, Wanli" sort="Liu, Wanli" uniqKey="Liu W" first="Wanli" last="Liu">Wanli Liu</name>
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<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Song, Wenxia" sort="Song, Wenxia" uniqKey="Song W" first="Wenxia" last="Song">Wenxia Song</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland</wicri:regionArea>
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<settlement type="city">College Park (Maryland)</settlement>
</placeName>
<orgName type="university">Université du Maryland</orgName>
</affiliation>
</author>
<author><name sortKey="Zhao, Xiaodong" sort="Zhao, Xiaodong" uniqKey="Zhao X" first="Xiaodong" last="Zhao">Xiaodong Zhao</name>
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<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
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<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
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<author><name sortKey="Liu, Chaohong" sort="Liu, Chaohong" uniqKey="Liu C" first="Chaohong" last="Liu">Chaohong Liu</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.</title>
<author><name sortKey="Huang, Lu" sort="Huang, Lu" uniqKey="Huang L" first="Lu" last="Huang">Lu Huang</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
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<author><name sortKey="Zhang, Yongjie" sort="Zhang, Yongjie" uniqKey="Zhang Y" first="Yongjie" last="Zhang">Yongjie Zhang</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xu, Chenguang" sort="Xu, Chenguang" uniqKey="Xu C" first="Chenguang" last="Xu">Chenguang Xu</name>
<affiliation wicri:level="3"><nlm:affiliation>MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gu, Xiaomei" sort="Gu, Xiaomei" uniqKey="Gu X" first="Xiaomei" last="Gu">Xiaomei Gu</name>
<affiliation wicri:level="3"><nlm:affiliation>MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Niu, Linlin" sort="Niu, Linlin" uniqKey="Niu L" first="Linlin" last="Niu">Linlin Niu</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Jinzhi" sort="Wang, Jinzhi" uniqKey="Wang J" first="Jinzhi" last="Wang">Jinzhi Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sun, Xiaoyu" sort="Sun, Xiaoyu" uniqKey="Sun X" first="Xiaoyu" last="Sun">Xiaoyu Sun</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bai, Xiaoming" sort="Bai, Xiaoming" uniqKey="Bai X" first="Xiaoming" last="Bai">Xiaoming Bai</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xuan, Xingtian" sort="Xuan, Xingtian" uniqKey="Xuan X" first="Xingtian" last="Xuan">Xingtian Xuan</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Li, Qubei" sort="Li, Qubei" uniqKey="Li Q" first="Qubei" last="Li">Qubei Li</name>
<affiliation wicri:level="1"><nlm:affiliation>Children's Hospital Respiratory Center of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Children's Hospital Respiratory Center of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Shi, Chunwei" sort="Shi, Chunwei" uniqKey="Shi C" first="Chunwei" last="Shi">Chunwei Shi</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yu, Bing" sort="Yu, Bing" uniqKey="Yu B" first="Bing" last="Yu">Bing Yu</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Miller, Heather" sort="Miller, Heather" uniqKey="Miller H" first="Heather" last="Miller">Heather Miller</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Intracellular Pathogens, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Intracellular Pathogens, National Institute of Allergy and Infectious Diseases, Hamilton, Montana</wicri:regionArea>
<placeName><region type="state">Montana</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, Gangyi" sort="Yang, Gangyi" uniqKey="Yang G" first="Gangyi" last="Yang">Gangyi Yang</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Westerberg, Lisa S" sort="Westerberg, Lisa S" uniqKey="Westerberg L" first="Lisa S" last="Westerberg">Lisa S. Westerberg</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea>
<placeName><settlement type="city">Stockholm</settlement>
<region nuts="2">Svealand</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Liu, Wanli" sort="Liu, Wanli" uniqKey="Liu W" first="Wanli" last="Liu">Wanli Liu</name>
<affiliation wicri:level="3"><nlm:affiliation>MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Song, Wenxia" sort="Song, Wenxia" uniqKey="Song W" first="Wenxia" last="Song">Wenxia Song</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland</wicri:regionArea>
<placeName><region type="state">Maryland</region>
<settlement type="city">College Park (Maryland)</settlement>
</placeName>
<orgName type="university">Université du Maryland</orgName>
</affiliation>
</author>
<author><name sortKey="Zhao, Xiaodong" sort="Zhao, Xiaodong" uniqKey="Zhao X" first="Xiaodong" last="Zhao">Xiaodong Zhao</name>
<affiliation wicri:level="1"><nlm:affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing</wicri:regionArea>
<wicri:noRegion>Chongqing</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liu, Chaohong" sort="Liu, Chaohong" uniqKey="Liu C" first="Chaohong" last="Liu">Chaohong Liu</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS biology</title>
<idno type="eISSN">1545-7885</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Actins (metabolism)</term>
<term>Agammaglobulinaemia Tyrosine Kinase (MeSH)</term>
<term>Animals (MeSH)</term>
<term>B-Lymphocytes (metabolism)</term>
<term>Bridged Bicyclo Compounds, Heterocyclic (MeSH)</term>
<term>Carrier Proteins (metabolism)</term>
<term>Cell Membrane (metabolism)</term>
<term>Cytoskeletal Proteins (metabolism)</term>
<term>Immunity, Humoral (MeSH)</term>
<term>Male (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Mice, Knockout (MeSH)</term>
<term>Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases (metabolism)</term>
<term>Polymerization (MeSH)</term>
<term>Protein-Tyrosine Kinases (metabolism)</term>
<term>Rapamycin-Insensitive Companion of mTOR Protein (MeSH)</term>
<term>Thiazolidines (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Actines (métabolisme)</term>
<term>Agammaglobulinaemia tyrosine kinase (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Compagnon de mTOR insensible à la rapamycine (MeSH)</term>
<term>Composés hétérocycliques bicycliques (MeSH)</term>
<term>Immunité humorale (MeSH)</term>
<term>Lymphocytes B (métabolisme)</term>
<term>Membrane cellulaire (métabolisme)</term>
<term>Mâle (MeSH)</term>
<term>Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatases (métabolisme)</term>
<term>Polymérisation (MeSH)</term>
<term>Protein-tyrosine kinases (métabolisme)</term>
<term>Protéines de transport (métabolisme)</term>
<term>Protéines du cytosquelette (métabolisme)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Souris knockout (MeSH)</term>
<term>Thiazolidines (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Actins</term>
<term>Carrier Proteins</term>
<term>Cytoskeletal Proteins</term>
<term>Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases</term>
<term>Protein-Tyrosine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Agammaglobulinaemia Tyrosine Kinase</term>
<term>Bridged Bicyclo Compounds, Heterocyclic</term>
<term>Rapamycin-Insensitive Companion of mTOR Protein</term>
<term>Thiazolidines</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>B-Lymphocytes</term>
<term>Cell Membrane</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Actines</term>
<term>Lymphocytes B</term>
<term>Membrane cellulaire</term>
<term>Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatases</term>
<term>Protein-tyrosine kinases</term>
<term>Protéines de transport</term>
<term>Protéines du cytosquelette</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Immunity, Humoral</term>
<term>Male</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Polymerization</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Agammaglobulinaemia tyrosine kinase</term>
<term>Animaux</term>
<term>Compagnon de mTOR insensible à la rapamycine</term>
<term>Composés hétérocycliques bicycliques</term>
<term>Immunité humorale</term>
<term>Mâle</term>
<term>Polymérisation</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Thiazolidines</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling. We found that the key positive and negative BCR signaling molecules, phosphorylated Brutons tyrosine kinase (pBtk) and phosphorylated SH2-containing inositol phosphatase (pSHIP), are reduced and enhanced, respectively, in Rictor KO B cells. This suggests that Rictor positively regulates the early events of BCR signaling. We found that the cellular filamentous actin (F-actin) is drastically increased in Rictor KO B cells after BCR stimulation through dysregulating the dephosphorylation of ezrin. The high actin-ezrin intensity area restricts the lateral movement of BCRs upon stimulation, consequently reducing BCR clustering and BCR signaling. The reduction in the initiation of BCR signaling caused by actin alteration is associated with a decreased humoral immune response in Rictor KO mice. The inhibition of actin polymerization with latrunculin in Rictor KO B cells rescues the defects of BCR signaling and B cell differentiation. Overall, our study provides a new pathway linking cell metablism to BCR activation, in which Rictor regulates BCR signaling via actin reorganization.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28821013</PMID>
<DateCompleted><Year>2017</Year>
<Month>09</Month>
<Day>27</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>12</Month>
<Day>02</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1545-7885</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>15</Volume>
<Issue>8</Issue>
<PubDate><Year>2017</Year>
<Month>Aug</Month>
</PubDate>
</JournalIssue>
<Title>PLoS biology</Title>
<ISOAbbreviation>PLoS Biol</ISOAbbreviation>
</Journal>
<ArticleTitle>Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.</ArticleTitle>
<Pagination><MedlinePgn>e2001750</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pbio.2001750</ELocationID>
<Abstract><AbstractText>As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling. We found that the key positive and negative BCR signaling molecules, phosphorylated Brutons tyrosine kinase (pBtk) and phosphorylated SH2-containing inositol phosphatase (pSHIP), are reduced and enhanced, respectively, in Rictor KO B cells. This suggests that Rictor positively regulates the early events of BCR signaling. We found that the cellular filamentous actin (F-actin) is drastically increased in Rictor KO B cells after BCR stimulation through dysregulating the dephosphorylation of ezrin. The high actin-ezrin intensity area restricts the lateral movement of BCRs upon stimulation, consequently reducing BCR clustering and BCR signaling. The reduction in the initiation of BCR signaling caused by actin alteration is associated with a decreased humoral immune response in Rictor KO mice. The inhibition of actin polymerization with latrunculin in Rictor KO B cells rescues the defects of BCR signaling and B cell differentiation. Overall, our study provides a new pathway linking cell metablism to BCR activation, in which Rictor regulates BCR signaling via actin reorganization.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Huang</LastName>
<ForeName>Lu</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Yongjie</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.</Affiliation>
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<name sortKey="Wang, Jinzhi" sort="Wang, Jinzhi" uniqKey="Wang J" first="Jinzhi" last="Wang">Jinzhi Wang</name>
<name sortKey="Wang, Jinzhi" sort="Wang, Jinzhi" uniqKey="Wang J" first="Jinzhi" last="Wang">Jinzhi Wang</name>
<name sortKey="Xu, Chenguang" sort="Xu, Chenguang" uniqKey="Xu C" first="Chenguang" last="Xu">Chenguang Xu</name>
<name sortKey="Xuan, Xingtian" sort="Xuan, Xingtian" uniqKey="Xuan X" first="Xingtian" last="Xuan">Xingtian Xuan</name>
<name sortKey="Xuan, Xingtian" sort="Xuan, Xingtian" uniqKey="Xuan X" first="Xingtian" last="Xuan">Xingtian Xuan</name>
<name sortKey="Xuan, Xingtian" sort="Xuan, Xingtian" uniqKey="Xuan X" first="Xingtian" last="Xuan">Xingtian Xuan</name>
<name sortKey="Yang, Gangyi" sort="Yang, Gangyi" uniqKey="Yang G" first="Gangyi" last="Yang">Gangyi Yang</name>
<name sortKey="Yu, Bing" sort="Yu, Bing" uniqKey="Yu B" first="Bing" last="Yu">Bing Yu</name>
<name sortKey="Zhang, Yongjie" sort="Zhang, Yongjie" uniqKey="Zhang Y" first="Yongjie" last="Zhang">Yongjie Zhang</name>
<name sortKey="Zhang, Yongjie" sort="Zhang, Yongjie" uniqKey="Zhang Y" first="Yongjie" last="Zhang">Yongjie Zhang</name>
<name sortKey="Zhang, Yongjie" sort="Zhang, Yongjie" uniqKey="Zhang Y" first="Yongjie" last="Zhang">Yongjie Zhang</name>
<name sortKey="Zhao, Xiaodong" sort="Zhao, Xiaodong" uniqKey="Zhao X" first="Xiaodong" last="Zhao">Xiaodong Zhao</name>
<name sortKey="Zhao, Xiaodong" sort="Zhao, Xiaodong" uniqKey="Zhao X" first="Xiaodong" last="Zhao">Xiaodong Zhao</name>
<name sortKey="Zhao, Xiaodong" sort="Zhao, Xiaodong" uniqKey="Zhao X" first="Xiaodong" last="Zhao">Xiaodong Zhao</name>
</country>
<country name="États-Unis"><region name="Montana"><name sortKey="Miller, Heather" sort="Miller, Heather" uniqKey="Miller H" first="Heather" last="Miller">Heather Miller</name>
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<name sortKey="Song, Wenxia" sort="Song, Wenxia" uniqKey="Song W" first="Wenxia" last="Song">Wenxia Song</name>
</country>
<country name="Suède"><region name="Svealand"><name sortKey="Westerberg, Lisa S" sort="Westerberg, Lisa S" uniqKey="Westerberg L" first="Lisa S" last="Westerberg">Lisa S. Westerberg</name>
</region>
</country>
</tree>
</affiliations>
</record>

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   |wiki=    Bois
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   |clé=     pubmed:28821013
   |texte=   Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.
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	Serveur d'exploration sur la rapamycine et les champignons
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur la rapamycine et les champignons

Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.

Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.

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