Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry

Research output: Contribution to journalArticle

Abstract

Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets. As a functional consequence, RTN4-depleted cells fail to sustain elevated cytoplasmic Ca(2+) levels via SOCE and therefor are less susceptible to Ca(2+) overload induced apoptosis. Thus, for the first time, our results show a direct correlation between ER morphology and SOCE and highlight the importance of RTN4 in cellular Ca(2+) homeostasis.

Details

Authors
  • Levente Jozsef
  • Keitaro Tashiro
  • Andrew Kuo
  • Eon Joo Park
  • Athanasia Skoura
  • Sebastian Albinsson
  • Felix Rivera-Molina
  • Kenneth D Harrison
  • Yasuko Iwakiri
  • Derek Toomre
  • William C Sessa
External organisations
  • Yale University
Research areas and keywords

Keywords

  • Animals, Apoptosis, Calcium, Calcium Channels, Cell Line, Endoplasmic Reticulum, GPI-Linked Proteins, Gene Knockout Techniques, Homeostasis, Membrane Glycoproteins, Mice, Myelin Proteins, Receptors, Cell Surface
Original languageEnglish
Pages (from-to)9380-95
Number of pages16
JournalJournal of Biological Chemistry
Volume289
Issue number13
Publication statusPublished - 2014 Mar 28
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes