Abstract：
:Pancreatic β cells secrete insulin by Ca2+-triggered exocytosis. However, there is no apparent secretory site similar to the neuronal active zones, and the cellular and molecular localization mechanism underlying polarized exocytosis remains elusive. Here, we report that ELKS, a vertebrate active zone protein, is used in β cells to regulate Ca2+ influx for insulin secretion. β cell-specific ELKS-knockout (KO) mice showed impaired glucose-stimulated first-phase insulin secretion and reduced L-type voltage-dependent Ca2+ channel (VDCC) current density. In situ Ca2+ imaging of β cells within islets expressing a membrane-bound G-CaMP8b Ca2+ sensor demonstrated initial local Ca2+ signals at the ELKS-localized vascular side of the β cell plasma membrane, which were markedly decreased in ELKS-KO β cells. Mechanistically, ELKS directly interacted with the VDCC-β subunit via the GK domain. These findings suggest that ELKS and VDCCs form a potent insulin secretion complex at the vascular side of the β cell plasma membrane for polarized Ca2+ influx and first-phase insulin secretion from pancreatic islets.
journal_name
Cell Repjournal_title
Cell reportsauthors
Ohara-Imaizumi M,Aoyagi K,Yamauchi H,Yoshida M,Mori MX,Hida Y,Tran HN,Ohkura M,Abe M,Akimoto Y,Nakamichi Y,Nishiwaki C,Kawakami H,Hara K,Sakimura K,Nagamatsu S,Mori Y,Nakai J,Kakei M,Ohtsuka Tdoi
10.1016/j.celrep.2018.12.106subject
Has Abstractpub_date
2019-01-29 00:00:00pages
1213-1226.e7issue
5issn
2211-1247pii
S2211-1247(18)32081-3journal_volume
26pub_type
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