Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion.
The exocyst complex subunit Sec5 is a downstream effector of RalA-GTPase which promotes RalA-exocyst interactions and exocyst assembly, serving to tether secretory granules to docking sites on the plasma membrane. We recently reported that RalA regulates biphasic insulin secretion in pancreatic isle...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3699660?pdf=render |
| _version_ | 1811322639124267008 |
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| author | Li Xie Dan Zhu Youhou Kang Tao Liang Yu He Herbert Y Gaisano |
| author_facet | Li Xie Dan Zhu Youhou Kang Tao Liang Yu He Herbert Y Gaisano |
| author_sort | Li Xie |
| collection | DOAJ |
| description | The exocyst complex subunit Sec5 is a downstream effector of RalA-GTPase which promotes RalA-exocyst interactions and exocyst assembly, serving to tether secretory granules to docking sites on the plasma membrane. We recently reported that RalA regulates biphasic insulin secretion in pancreatic islet β cells in part by tethering insulin secretory granules to Ca(2+) channels to assist excitosome assembly. Here, we assessed β cell exocytosis by patch clamp membrane capacitance measurement and total internal reflection fluorescence microscopy to investigate the role of Sec5 in regulating insulin secretion. Sec5 is present in human and rodent islet β cells, localized to insulin granules. Sec5 protein depletion in rat INS-1 cells inhibited depolarization-induced release of primed insulin granules from both readily-releasable pool and mobilization from the reserve pool. This reduction in insulin exocytosis was attributed mainly to reduction in recruitment and exocytosis of newcomer insulin granules that undergo minimal docking time at the plasma membrane, but which encompassed a larger portion of biphasic glucose stimulated insulin secretion. Sec5 protein knockdown had little effect on predocked granules, unless vigorously stimulated by KCl depolarization. Taken together, newcomer insulin granules in β cells are more sensitive than predocked granules to Sec5 regulation. |
| first_indexed | 2024-04-13T13:38:36Z |
| format | Article |
| id | doaj.art-ed33d249fe4d435bacbdda39b62f2d86 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:38:36Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ed33d249fe4d435bacbdda39b62f2d862022-12-22T02:44:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6756110.1371/journal.pone.0067561Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion.Li XieDan ZhuYouhou KangTao LiangYu HeHerbert Y GaisanoThe exocyst complex subunit Sec5 is a downstream effector of RalA-GTPase which promotes RalA-exocyst interactions and exocyst assembly, serving to tether secretory granules to docking sites on the plasma membrane. We recently reported that RalA regulates biphasic insulin secretion in pancreatic islet β cells in part by tethering insulin secretory granules to Ca(2+) channels to assist excitosome assembly. Here, we assessed β cell exocytosis by patch clamp membrane capacitance measurement and total internal reflection fluorescence microscopy to investigate the role of Sec5 in regulating insulin secretion. Sec5 is present in human and rodent islet β cells, localized to insulin granules. Sec5 protein depletion in rat INS-1 cells inhibited depolarization-induced release of primed insulin granules from both readily-releasable pool and mobilization from the reserve pool. This reduction in insulin exocytosis was attributed mainly to reduction in recruitment and exocytosis of newcomer insulin granules that undergo minimal docking time at the plasma membrane, but which encompassed a larger portion of biphasic glucose stimulated insulin secretion. Sec5 protein knockdown had little effect on predocked granules, unless vigorously stimulated by KCl depolarization. Taken together, newcomer insulin granules in β cells are more sensitive than predocked granules to Sec5 regulation.http://europepmc.org/articles/PMC3699660?pdf=render |
| spellingShingle | Li Xie Dan Zhu Youhou Kang Tao Liang Yu He Herbert Y Gaisano Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion. PLoS ONE |
| title | Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion. |
| title_full | Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion. |
| title_fullStr | Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion. |
| title_full_unstemmed | Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion. |
| title_short | Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion. |
| title_sort | exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion |
| url | http://europepmc.org/articles/PMC3699660?pdf=render |
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