Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels

  • Rana A
  • Yen M
  • Sadaghiani A
 et al. 
  • 58

    Readers

    Mendeley users who have this article in their library.
  • 31

    Citations

    Citations of this article.

Abstract

Store-operated calcium entry (SOCE) regulates a wide variety of essential cellular functions. SOCE is mediated by STIM1 and STIM2, which sense depletion of ER Ca(2+) stores and activate Orai channels in the plasma membrane. Although the amplitude and dynamics of SOCE are considered important determinants of Ca(2+)-dependent responses, the underlying modulatory mechanisms are unclear. In this paper, we identify STIM2β, a highly conserved alternatively spliced isoform of STIM2, which, in contrast to all known STIM isoforms, is a potent inhibitor of SOCE. Although STIM2β does not by itself strongly bind Orai1, it is recruited to Orai1 channels by forming heterodimers with other STIM isoforms. Analysis of STIM2β mutants and Orai1-STIM2β chimeras suggested that it actively inhibits SOCE through a sequence-specific allosteric interaction with Orai1. Our results reveal a previously unrecognized functional flexibility in the STIM protein family by which alternative splicing creates negative and positive regulators of SOCE to shape the amplitude and dynamics of Ca(2+) signals.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Anshul Rana

  • Michelle Yen

  • Amir Masoud Sadaghiani

  • Chan Young Park

  • Ricardo E. Dolmetsch

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free