Regulation and Quality Control of Adiponectin Assembly by Endoplasmic Reticulum Chaperone ERp44.
Identifieur interne : 001593 ( Main/Exploration ); précédent : 001592; suivant : 001594Regulation and Quality Control of Adiponectin Assembly by Endoplasmic Reticulum Chaperone ERp44.
Auteurs : Lutz Hampe ; Mazdak Radjainia ; Cheng Xu [République populaire de Chine] ; Paul W R. Harris [Nouvelle-Zélande] ; Ghader Bashiri ; David C. Goldstone ; Margaret A. Brimble [Nouvelle-Zélande] ; Yu Wang [République populaire de Chine] ; Alok K. Mitra [Nouvelle-Zélande]Source :
- The Journal of biological chemistry [ 1083-351X ] ; 2015.
Descripteurs français
- KwdFr :
- Adiponectine (), Adiponectine (métabolisme), Animaux, Cartes d'interactions protéiques, Cellules HEK293, Chaperons moléculaires (métabolisme), Données de séquences moléculaires, Humains, Liaison aux protéines, Multimérisation de protéines, Protéines membranaires (métabolisme), Réticulum endoplasmique (métabolisme), Souris, Séquence d'acides aminés.
- MESH :
- métabolisme : Adiponectine, Chaperons moléculaires, Protéines membranaires, Réticulum endoplasmique.
- Adiponectine, Animaux, Cartes d'interactions protéiques, Cellules HEK293, Données de séquences moléculaires, Humains, Liaison aux protéines, Multimérisation de protéines, Souris, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Adiponectin (chemistry), Adiponectin (metabolism), Amino Acid Sequence, Animals, Endoplasmic Reticulum (metabolism), HEK293 Cells, Humans, Membrane Proteins (metabolism), Mice, Molecular Chaperones (metabolism), Molecular Sequence Data, Protein Binding, Protein Interaction Maps, Protein Multimerization.
- MESH :
- chemical , chemistry : Adiponectin.
- chemical , metabolism : Adiponectin, Membrane Proteins, Molecular Chaperones.
- metabolism : Endoplasmic Reticulum.
- Amino Acid Sequence, Animals, HEK293 Cells, Humans, Mice, Molecular Sequence Data, Protein Binding, Protein Interaction Maps, Protein Multimerization.
Abstract
Adiponectin, a collagenous hormone secreted abundantly from adipocytes, possesses potent antidiabetic and anti-inflammatory properties. Mediated by the conserved Cys(39) located in the variable region of the N terminus, the trimeric (low molecular weight (LMW)) adiponectin subunit assembles into different higher order complexes, e.g. hexamers (middle molecular weight (MMW)) and 12-18-mers (high molecular weight (HMW)), the latter being mostly responsible for the insulin-sensitizing activity of adiponectin. The endoplasmic reticulum (ER) chaperone ERp44 retains adiponectin in the early secretory compartment and tightly controls the oxidative state of Cys(39) and the oligomerization of adiponectin. Using cellular and in vitro assays, we show that ERp44 specifically recognizes the LMW and MMW forms but not the HMW form. Our binding assays with short peptide mimetics of adiponectin suggest that ERp44 intercepts and converts the pool of fully oxidized LMW and MMW adiponectin, but not the HMW form, into reduced trimeric precursors. These ERp44-bound precursors in the cis-Golgi may be transported back to the ER and released to enhance the population of adiponectin intermediates with appropriate oxidative state for HMW assembly, thereby underpinning the process of ERp44 quality control.
DOI: 10.1074/jbc.M115.663088
PubMed: 26060250
Affiliations:
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Mitra</name><affiliation wicri:level="1"><nlm:affiliation>From the School of Biological Science and a.mitra@auckland.ac.nz.</nlm:affiliation><country wicri:rule="url">Nouvelle-Zélande</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26060250</idno><idno type="pmid">26060250</idno><idno type="doi">10.1074/jbc.M115.663088</idno><idno type="wicri:Area/PubMed/Corpus">001602</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001602</idno><idno type="wicri:Area/PubMed/Curation">001602</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001602</idno><idno type="wicri:Area/PubMed/Checkpoint">001366</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001366</idno><idno type="wicri:Area/Ncbi/Merge">001138</idno><idno type="wicri:Area/Ncbi/Curation">001138</idno><idno type="wicri:Area/Ncbi/Checkpoint">001138</idno><idno type="wicri:Area/Main/Merge">001598</idno><idno type="wicri:Area/Main/Curation">001593</idno><idno type="wicri:Area/Main/Exploration">001593</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Regulation and Quality Control of Adiponectin Assembly by Endoplasmic Reticulum Chaperone ERp44.</title><author><name sortKey="Hampe, Lutz" sort="Hampe, Lutz" uniqKey="Hampe L" first="Lutz" last="Hampe">Lutz Hampe</name><affiliation><nlm:affiliation>From the School of Biological Science and.</nlm:affiliation><wicri:noCountry code="no comma">From the School of Biological Science and.</wicri:noCountry></affiliation></author><author><name sortKey="Radjainia, Mazdak" sort="Radjainia, Mazdak" uniqKey="Radjainia M" first="Mazdak" last="Radjainia">Mazdak Radjainia</name><affiliation><nlm:affiliation>From the School of Biological Science and.</nlm:affiliation><wicri:noCountry code="no comma">From the School of Biological Science and.</wicri:noCountry></affiliation></author><author><name sortKey="Xu, Cheng" sort="Xu, Cheng" uniqKey="Xu C" first="Cheng" last="Xu">Cheng Xu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Pharmaceutical Biotechnology and Department of Pharmacology and Pharmacy, The University of Hong Kong, 999007 Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology and Department of Pharmacology and Pharmacy, The University of Hong Kong, 999007 Hong Kong</wicri:regionArea><wicri:noRegion>999007 Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Harris, Paul W R" sort="Harris, Paul W R" uniqKey="Harris P" first="Paul W R" last="Harris">Paul W R. Harris</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand, and Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand, Institute for Innovation in Biotechnology, The University of Auckland, 3A Symonds Street, Auckland 1010, New Zealand.</nlm:affiliation><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand, and Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand, Institute for Innovation in Biotechnology, The University of Auckland, 3A Symonds Street, Auckland 1010</wicri:regionArea><wicri:noRegion>Auckland 1010</wicri:noRegion></affiliation></author><author><name sortKey="Bashiri, Ghader" sort="Bashiri, Ghader" uniqKey="Bashiri G" first="Ghader" last="Bashiri">Ghader Bashiri</name><affiliation><nlm:affiliation>From the School of Biological Science and.</nlm:affiliation><wicri:noCountry code="no comma">From the School of Biological Science and.</wicri:noCountry></affiliation></author><author><name sortKey="Goldstone, David C" sort="Goldstone, David C" uniqKey="Goldstone D" first="David C" last="Goldstone">David C. Goldstone</name><affiliation><nlm:affiliation>From the School of Biological Science and.</nlm:affiliation><wicri:noCountry code="no comma">From the School of Biological Science and.</wicri:noCountry></affiliation></author><author><name sortKey="Brimble, Margaret A" sort="Brimble, Margaret A" uniqKey="Brimble M" first="Margaret A" last="Brimble">Margaret A. Brimble</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand, and Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand, Institute for Innovation in Biotechnology, The University of Auckland, 3A Symonds Street, Auckland 1010, New Zealand.</nlm:affiliation><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand, and Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1010, New Zealand, Institute for Innovation in Biotechnology, The University of Auckland, 3A Symonds Street, Auckland 1010</wicri:regionArea><wicri:noRegion>Auckland 1010</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Pharmaceutical Biotechnology and Department of Pharmacology and Pharmacy, The University of Hong Kong, 999007 Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology and Department of Pharmacology and Pharmacy, The University of Hong Kong, 999007 Hong Kong</wicri:regionArea><wicri:noRegion>999007 Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Mitra, Alok K" sort="Mitra, Alok K" uniqKey="Mitra A" first="Alok K" last="Mitra">Alok K. Mitra</name><affiliation wicri:level="1"><nlm:affiliation>From the School of Biological Science and a.mitra@auckland.ac.nz.</nlm:affiliation><country wicri:rule="url">Nouvelle-Zélande</country></affiliation></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adiponectin (chemistry)</term><term>Adiponectin (metabolism)</term><term>Amino Acid Sequence</term><term>Animals</term><term>Endoplasmic Reticulum (metabolism)</term><term>HEK293 Cells</term><term>Humans</term><term>Membrane Proteins (metabolism)</term><term>Mice</term><term>Molecular Chaperones (metabolism)</term><term>Molecular Sequence Data</term><term>Protein Binding</term><term>Protein Interaction Maps</term><term>Protein Multimerization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adiponectine ()</term><term>Adiponectine (métabolisme)</term><term>Animaux</term><term>Cartes d'interactions protéiques</term><term>Cellules HEK293</term><term>Chaperons moléculaires (métabolisme)</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Liaison aux protéines</term><term>Multimérisation de protéines</term><term>Protéines membranaires (métabolisme)</term><term>Réticulum endoplasmique (métabolisme)</term><term>Souris</term><term>Séquence d'acides aminés</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Adiponectin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adiponectin</term><term>Membrane Proteins</term><term>Molecular Chaperones</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endoplasmic Reticulum</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Adiponectine</term><term>Chaperons moléculaires</term><term>Protéines membranaires</term><term>Réticulum endoplasmique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>HEK293 Cells</term><term>Humans</term><term>Mice</term><term>Molecular Sequence Data</term><term>Protein Binding</term><term>Protein Interaction Maps</term><term>Protein Multimerization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adiponectine</term><term>Animaux</term><term>Cartes d'interactions protéiques</term><term>Cellules HEK293</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Liaison aux protéines</term><term>Multimérisation de protéines</term><term>Souris</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Adiponectin, a collagenous hormone secreted abundantly from adipocytes, possesses potent antidiabetic and anti-inflammatory properties. Mediated by the conserved Cys(39) located in the variable region of the N terminus, the trimeric (low molecular weight (LMW)) adiponectin subunit assembles into different higher order complexes, e.g. hexamers (middle molecular weight (MMW)) and 12-18-mers (high molecular weight (HMW)), the latter being mostly responsible for the insulin-sensitizing activity of adiponectin. The endoplasmic reticulum (ER) chaperone ERp44 retains adiponectin in the early secretory compartment and tightly controls the oxidative state of Cys(39) and the oligomerization of adiponectin. Using cellular and in vitro assays, we show that ERp44 specifically recognizes the LMW and MMW forms but not the HMW form. Our binding assays with short peptide mimetics of adiponectin suggest that ERp44 intercepts and converts the pool of fully oxidized LMW and MMW adiponectin, but not the HMW form, into reduced trimeric precursors. These ERp44-bound precursors in the cis-Golgi may be transported back to the ER and released to enhance the population of adiponectin intermediates with appropriate oxidative state for HMW assembly, thereby underpinning the process of ERp44 quality control. </div></front></TEI><affiliations><list><country><li>Nouvelle-Zélande</li><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Bashiri, Ghader" sort="Bashiri, Ghader" uniqKey="Bashiri G" first="Ghader" last="Bashiri">Ghader Bashiri</name><name sortKey="Goldstone, David C" sort="Goldstone, David C" uniqKey="Goldstone D" first="David C" last="Goldstone">David C. Goldstone</name><name sortKey="Hampe, Lutz" sort="Hampe, Lutz" uniqKey="Hampe L" first="Lutz" last="Hampe">Lutz Hampe</name><name sortKey="Radjainia, Mazdak" sort="Radjainia, Mazdak" uniqKey="Radjainia M" first="Mazdak" last="Radjainia">Mazdak Radjainia</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Xu, Cheng" sort="Xu, Cheng" uniqKey="Xu C" first="Cheng" last="Xu">Cheng Xu</name></noRegion><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name></country><country name="Nouvelle-Zélande"><noRegion><name sortKey="Harris, Paul W R" sort="Harris, Paul W R" uniqKey="Harris P" first="Paul W R" last="Harris">Paul W R. Harris</name></noRegion><name sortKey="Brimble, Margaret A" sort="Brimble, Margaret A" uniqKey="Brimble M" first="Margaret A" last="Brimble">Margaret A. Brimble</name><name sortKey="Mitra, Alok K" sort="Mitra, Alok K" uniqKey="Mitra A" first="Alok K" last="Mitra">Alok K. 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