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The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane
Granuphilin, an effector of the small GTPase Rab27a, mediates the stable attachment (docking) of insulin granules to the plasma membrane and inhibits subsequent fusion of docked granules, possibly through interaction with a fusion-inhibitory Munc18-1/syntaxin complex. However, phenotypes of insulin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564536/ https://www.ncbi.nlm.nih.gov/pubmed/23223571 http://dx.doi.org/10.1091/mbc.E12-04-0265 |
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author | Wang, Hao Ishizaki, Ray Xu, Jun Kasai, Kazuo Kobayashi, Eri Gomi, Hiroshi Izumi, Tetsuro |
author_facet | Wang, Hao Ishizaki, Ray Xu, Jun Kasai, Kazuo Kobayashi, Eri Gomi, Hiroshi Izumi, Tetsuro |
author_sort | Wang, Hao |
collection | PubMed |
description | Granuphilin, an effector of the small GTPase Rab27a, mediates the stable attachment (docking) of insulin granules to the plasma membrane and inhibits subsequent fusion of docked granules, possibly through interaction with a fusion-inhibitory Munc18-1/syntaxin complex. However, phenotypes of insulin exocytosis differ considerably between Rab27a- and granuphilin-deficient pancreatic β cells, suggesting that other Rab27a effectors function in those cells. We found that one of the putative Rab27a effector family proteins, exophilin7/JFC1/Slp1, is expressed in β cells; however, unlike granuphilin, exophilin7 overexpressed in the β-cell line MIN6 failed to show granule-docking or fusion-inhibitory activity. Furthermore, exophilin7 has no affinities to either Munc18-1 or Munc18-1–interacting syntaxin-1a, in contrast to granuphilin. Although β cells of exophilin7-knockout mice show no apparent abnormalities in intracellular distribution or in ordinary glucose-induced exocytosis of insulin granules, they do show impaired fusion in response to some stronger stimuli, specifically from granules that have not been docked to the plasma membrane. Exophilin7 appears to mediate the fusion of undocked granules through the affinity of its C2A domain toward the plasma membrane phospholipids. These findings indicate that the two Rab27a effectors, granuphilin and exophilin7, differentially regulate the exocytosis of either stably or minimally docked granules, respectively. |
format | Online Article Text |
id | pubmed-3564536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35645362013-04-16 The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane Wang, Hao Ishizaki, Ray Xu, Jun Kasai, Kazuo Kobayashi, Eri Gomi, Hiroshi Izumi, Tetsuro Mol Biol Cell Articles Granuphilin, an effector of the small GTPase Rab27a, mediates the stable attachment (docking) of insulin granules to the plasma membrane and inhibits subsequent fusion of docked granules, possibly through interaction with a fusion-inhibitory Munc18-1/syntaxin complex. However, phenotypes of insulin exocytosis differ considerably between Rab27a- and granuphilin-deficient pancreatic β cells, suggesting that other Rab27a effectors function in those cells. We found that one of the putative Rab27a effector family proteins, exophilin7/JFC1/Slp1, is expressed in β cells; however, unlike granuphilin, exophilin7 overexpressed in the β-cell line MIN6 failed to show granule-docking or fusion-inhibitory activity. Furthermore, exophilin7 has no affinities to either Munc18-1 or Munc18-1–interacting syntaxin-1a, in contrast to granuphilin. Although β cells of exophilin7-knockout mice show no apparent abnormalities in intracellular distribution or in ordinary glucose-induced exocytosis of insulin granules, they do show impaired fusion in response to some stronger stimuli, specifically from granules that have not been docked to the plasma membrane. Exophilin7 appears to mediate the fusion of undocked granules through the affinity of its C2A domain toward the plasma membrane phospholipids. These findings indicate that the two Rab27a effectors, granuphilin and exophilin7, differentially regulate the exocytosis of either stably or minimally docked granules, respectively. The American Society for Cell Biology 2013-02-01 /pmc/articles/PMC3564536/ /pubmed/23223571 http://dx.doi.org/10.1091/mbc.E12-04-0265 Text en © 2013 Wang 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 Biology. |
spellingShingle | Articles Wang, Hao Ishizaki, Ray Xu, Jun Kasai, Kazuo Kobayashi, Eri Gomi, Hiroshi Izumi, Tetsuro The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane |
title | The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane |
title_full | The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane |
title_fullStr | The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane |
title_full_unstemmed | The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane |
title_short | The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane |
title_sort | rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564536/ https://www.ncbi.nlm.nih.gov/pubmed/23223571 http://dx.doi.org/10.1091/mbc.E12-04-0265 |
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