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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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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. |
format | Online Article Text |
id | pubmed-3496617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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