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Redox-dependent regulation of end-binding protein 1 activity by glutathionylation.

Identifieur interne : 000024 ( Main/Exploration ); précédent : 000023; suivant : 000025

Redox-dependent regulation of end-binding protein 1 activity by glutathionylation.

Auteurs : Miao Chen [République populaire de Chine] ; Jian Wang [République populaire de Chine] ; Yang Yang [République populaire de Chine] ; Tao Zhong [République populaire de Chine] ; Peng Zhou [République populaire de Chine] ; Huixian Ma [République populaire de Chine] ; Jingrui Li [République populaire de Chine] ; Dengwen Li [République populaire de Chine] ; Jun Zhou [République populaire de Chine] ; Songbo Xie [République populaire de Chine] ; Min Liu [République populaire de Chine]

Source :

RBID : pubmed:32737853

Abstract

Cytoskeletal proteins are susceptible to glutathionylation under oxidizing conditions, and oxidative damage has been implicated in several neurodegenerative diseases. End-binding protein 1 (EB1) is a master regulator of microtubule plus-end tracking proteins (+TIPs) and is critically involved in the control of microtubule dynamics and cellular processes. However, the impact of glutathionylation on EB1 functions remains unknown. Here we reveal that glutathionylation is important for controlling EB1 activity and protecting EB1 from irreversible oxidation. In vitro biochemical and cellular assays reveal that EB1 is glutathionylated. Diamide, a mild oxidizing reagent, reduces EB1 comet number and length in cells, indicating the impairment of microtubule dynamics. Three cysteine residues of EB1 are glutathionylated, with mutations of these three cysteines to serines attenuating microtubule dynamics but buffering diamide-induced decrease in microtubule dynamics. In addition, glutaredoxin 1 (Grx1) deglutathionylates EB1, and Grx1 depletion suppresses microtubule dynamics and leads to defects in cell division orientation and cell migration, suggesting a critical role of Grx1-mediated deglutathionylation in maintaining EB1 activity. Collectively, these data reveal that EB1 glutathionylation is an important protective mechanism for the regulation of microtubule dynamics and microtubule-based cellular activities.

DOI: 10.1007/s11427-020-1765-6
PubMed: 32737853


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<div type="abstract" xml:lang="en">Cytoskeletal proteins are susceptible to glutathionylation under oxidizing conditions, and oxidative damage has been implicated in several neurodegenerative diseases. End-binding protein 1 (EB1) is a master regulator of microtubule plus-end tracking proteins (+TIPs) and is critically involved in the control of microtubule dynamics and cellular processes. However, the impact of glutathionylation on EB1 functions remains unknown. Here we reveal that glutathionylation is important for controlling EB1 activity and protecting EB1 from irreversible oxidation. In vitro biochemical and cellular assays reveal that EB1 is glutathionylated. Diamide, a mild oxidizing reagent, reduces EB1 comet number and length in cells, indicating the impairment of microtubule dynamics. Three cysteine residues of EB1 are glutathionylated, with mutations of these three cysteines to serines attenuating microtubule dynamics but buffering diamide-induced decrease in microtubule dynamics. In addition, glutaredoxin 1 (Grx1) deglutathionylates EB1, and Grx1 depletion suppresses microtubule dynamics and leads to defects in cell division orientation and cell migration, suggesting a critical role of Grx1-mediated deglutathionylation in maintaining EB1 activity. Collectively, these data reveal that EB1 glutathionylation is an important protective mechanism for the regulation of microtubule dynamics and microtubule-based cellular activities.</div>
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<AbstractText>Cytoskeletal proteins are susceptible to glutathionylation under oxidizing conditions, and oxidative damage has been implicated in several neurodegenerative diseases. End-binding protein 1 (EB1) is a master regulator of microtubule plus-end tracking proteins (+TIPs) and is critically involved in the control of microtubule dynamics and cellular processes. However, the impact of glutathionylation on EB1 functions remains unknown. Here we reveal that glutathionylation is important for controlling EB1 activity and protecting EB1 from irreversible oxidation. In vitro biochemical and cellular assays reveal that EB1 is glutathionylated. Diamide, a mild oxidizing reagent, reduces EB1 comet number and length in cells, indicating the impairment of microtubule dynamics. Three cysteine residues of EB1 are glutathionylated, with mutations of these three cysteines to serines attenuating microtubule dynamics but buffering diamide-induced decrease in microtubule dynamics. In addition, glutaredoxin 1 (Grx1) deglutathionylates EB1, and Grx1 depletion suppresses microtubule dynamics and leads to defects in cell division orientation and cell migration, suggesting a critical role of Grx1-mediated deglutathionylation in maintaining EB1 activity. Collectively, these data reveal that EB1 glutathionylation is an important protective mechanism for the regulation of microtubule dynamics and microtubule-based cellular activities.</AbstractText>
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<Affiliation>Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China.</Affiliation>
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<Affiliation>Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China.</Affiliation>
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<ForeName>Jingrui</ForeName>
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<Affiliation>Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China.</Affiliation>
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<Initials>D</Initials>
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<AffiliationInfo>
<Affiliation>State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, 300071, China.</Affiliation>
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<Affiliation>Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China. xiesongbo@sdnu.edu.cn.</Affiliation>
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<AffiliationInfo>
<Affiliation>Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, China. minliu@sdnu.edu.cn.</Affiliation>
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<PublicationType UI="D016428">Journal Article</PublicationType>
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<ArticleDate DateType="Electronic">
<Year>2020</Year>
<Month>07</Month>
<Day>28</Day>
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<MedlineTA>Sci China Life Sci</MedlineTA>
<NlmUniqueID>101529880</NlmUniqueID>
<ISSNLinking>1674-7305</ISSNLinking>
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<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">cell division orientation</Keyword>
<Keyword MajorTopicYN="N">end-binding protein 1</Keyword>
<Keyword MajorTopicYN="N">glutaredoxin 1</Keyword>
<Keyword MajorTopicYN="N">glutathionylation</Keyword>
<Keyword MajorTopicYN="N">microtubule dynamics</Keyword>
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<PubMedPubDate PubStatus="received">
<Year>2020</Year>
<Month>02</Month>
<Day>29</Day>
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<Year>2020</Year>
<Month>06</Month>
<Day>23</Day>
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<Month>8</Month>
<Day>2</Day>
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<ArticleId IdType="pubmed">32737853</ArticleId>
<ArticleId IdType="doi">10.1007/s11427-020-1765-6</ArticleId>
<ArticleId IdType="pii">10.1007/s11427-020-1765-6</ArticleId>
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<li>République populaire de Chine</li>
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<country name="République populaire de Chine">
<noRegion>
<name sortKey="Chen, Miao" sort="Chen, Miao" uniqKey="Chen M" first="Miao" last="Chen">Miao Chen</name>
</noRegion>
<name sortKey="Li, Dengwen" sort="Li, Dengwen" uniqKey="Li D" first="Dengwen" last="Li">Dengwen Li</name>
<name sortKey="Li, Jingrui" sort="Li, Jingrui" uniqKey="Li J" first="Jingrui" last="Li">Jingrui Li</name>
<name sortKey="Liu, Min" sort="Liu, Min" uniqKey="Liu M" first="Min" last="Liu">Min Liu</name>
<name sortKey="Ma, Huixian" sort="Ma, Huixian" uniqKey="Ma H" first="Huixian" last="Ma">Huixian Ma</name>
<name sortKey="Wang, Jian" sort="Wang, Jian" uniqKey="Wang J" first="Jian" last="Wang">Jian Wang</name>
<name sortKey="Xie, Songbo" sort="Xie, Songbo" uniqKey="Xie S" first="Songbo" last="Xie">Songbo Xie</name>
<name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
<name sortKey="Zhong, Tao" sort="Zhong, Tao" uniqKey="Zhong T" first="Tao" last="Zhong">Tao Zhong</name>
<name sortKey="Zhou, Jun" sort="Zhou, Jun" uniqKey="Zhou J" first="Jun" last="Zhou">Jun Zhou</name>
<name sortKey="Zhou, Jun" sort="Zhou, Jun" uniqKey="Zhou J" first="Jun" last="Zhou">Jun Zhou</name>
<name sortKey="Zhou, Peng" sort="Zhou, Peng" uniqKey="Zhou P" first="Peng" last="Zhou">Peng Zhou</name>
</country>
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