ELKS/Voltage-Dependent Ca2+ Channel-β Subunit Module Regulates Polarized Ca2+ Influx in Pancreatic β Cells

Mica Ohara-Imaizumi, Kyota Aoyagi, Hajime Yamauchi, Masashi Yoshida, Masayuki X. Mori, Yamato Hida, Ha Nam Tran, Masamichi Ohkura, Manabu Abe, Yoshihiro Akimoto, Yoko Nakamichi, Chiyono Nishiwaki, Hayato Kawakami, Kazuo Hara, Kenji Sakimura, Shinya Nagamatsu, Yasuo Mori, Junichi Nakai, Masafumi Kakei, Toshihisa Ohtsuka

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1213-1226.e7
JournalCell Reports
Volume26
Issue number5
DOIs
Publication statusPublished - 2019 Jan 29

Keywords

  • Ca influx
  • ELKS
  • active zone protein
  • insulin exocytosis
  • pancreatic β cells
  • voltage-dependent Ca channel

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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