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MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway

Myosin- and Rab-interacting protein (MyRIP), which belongs to the protein kinase A (PKA)–anchoring family, is implicated in hormone secretion. However, its mechanism of action is not fully elucidated. Here we investigate the role of MyRIP in myosin Va (MyoVa)-dependent secretory granule (SG) transpo...

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Autores principales: Brozzi, Flora, Lajus, Sophie, Diraison, Frederique, Rajatileka, Shavanthi, Hayward, Katy, Regazzi, Romano, Molnár, Elek, Váradi, Anikó
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496617/
https://www.ncbi.nlm.nih.gov/pubmed/22993210
http://dx.doi.org/10.1091/mbc.E12-05-0369
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author Brozzi, Flora
Lajus, Sophie
Diraison, Frederique
Rajatileka, Shavanthi
Hayward, Katy
Regazzi, Romano
Molnár, Elek
Váradi, Anikó
author_facet Brozzi, Flora
Lajus, Sophie
Diraison, Frederique
Rajatileka, Shavanthi
Hayward, Katy
Regazzi, Romano
Molnár, Elek
Váradi, Anikó
author_sort Brozzi, Flora
collection PubMed
description Myosin- and Rab-interacting protein (MyRIP), which belongs to the protein kinase A (PKA)–anchoring family, is implicated in hormone secretion. However, its mechanism of action is not fully elucidated. Here we investigate the role of MyRIP in myosin Va (MyoVa)-dependent secretory granule (SG) transport and secretion in pancreatic beta cells. These cells solely express the brain isoform of MyoVa (BR-MyoVa), which is a key motor protein in SG transport. In vitro pull-down, coimmunoprecipitation, and colocalization studies revealed that MyRIP does not interact with BR-MyoVa in glucose-stimulated pancreatic beta cells, suggesting that, contrary to previous notions, MyRIP does not link this motor protein to SGs. Glucose-stimulated insulin secretion is augmented by incretin hormones, which increase cAMP levels and leads to MyRIP phosphorylation, its interaction with BR-MyoVa, and phosphorylation of the BR-MyoVa receptor rabphilin-3A (Rph-3A). Rph-3A phosphorylation on Ser-234 was inhibited by small interfering RNA knockdown of MyRIP, which also reduced cAMP-mediated hormone secretion. Demonstrating the importance of this phosphorylation, nonphosphorylatable and phosphomimic Rph-3A mutants significantly altered hormone release when PKA was activated. These data suggest that MyRIP only forms a functional protein complex with BR-MyoVa on SGs when cAMP is elevated and under this condition facilitates phosphorylation of SG-associated proteins, which in turn can enhance secretion.
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spelling pubmed-34966172013-01-30 MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway Brozzi, Flora Lajus, Sophie Diraison, Frederique Rajatileka, Shavanthi Hayward, Katy Regazzi, Romano Molnár, Elek Váradi, Anikó Mol Biol Cell Articles Myosin- and Rab-interacting protein (MyRIP), which belongs to the protein kinase A (PKA)–anchoring family, is implicated in hormone secretion. However, its mechanism of action is not fully elucidated. Here we investigate the role of MyRIP in myosin Va (MyoVa)-dependent secretory granule (SG) transport and secretion in pancreatic beta cells. These cells solely express the brain isoform of MyoVa (BR-MyoVa), which is a key motor protein in SG transport. In vitro pull-down, coimmunoprecipitation, and colocalization studies revealed that MyRIP does not interact with BR-MyoVa in glucose-stimulated pancreatic beta cells, suggesting that, contrary to previous notions, MyRIP does not link this motor protein to SGs. Glucose-stimulated insulin secretion is augmented by incretin hormones, which increase cAMP levels and leads to MyRIP phosphorylation, its interaction with BR-MyoVa, and phosphorylation of the BR-MyoVa receptor rabphilin-3A (Rph-3A). Rph-3A phosphorylation on Ser-234 was inhibited by small interfering RNA knockdown of MyRIP, which also reduced cAMP-mediated hormone secretion. Demonstrating the importance of this phosphorylation, nonphosphorylatable and phosphomimic Rph-3A mutants significantly altered hormone release when PKA was activated. These data suggest that MyRIP only forms a functional protein complex with BR-MyoVa on SGs when cAMP is elevated and under this condition facilitates phosphorylation of SG-associated proteins, which in turn can enhance secretion. The American Society for Cell Biology 2012-11-15 /pmc/articles/PMC3496617/ /pubmed/22993210 http://dx.doi.org/10.1091/mbc.E12-05-0369 Text en © 2012 Brozzi et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Brozzi, Flora
Lajus, Sophie
Diraison, Frederique
Rajatileka, Shavanthi
Hayward, Katy
Regazzi, Romano
Molnár, Elek
Váradi, Anikó
MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway
title MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway
title_full MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway
title_fullStr MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway
title_full_unstemmed MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway
title_short MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway
title_sort myrip interaction with myova on secretory granules is controlled by the camp-pka pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496617/
https://www.ncbi.nlm.nih.gov/pubmed/22993210
http://dx.doi.org/10.1091/mbc.E12-05-0369
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