Remodeling of ER-plasma membrane contact sites but not STIM1 phosphorylation inhibits Ca2+ influx in mitosis

Fang Yu, Satanay Zuhair Hubrack, Sumita Chakraborty, Lu Sun, Ethel Alcantara-Adap, Rashmi Kulkarni, Anja Billing, Johannes Graumann, Colin W. Taylor, Khaled Machaca

Research output: Contribution to journalArticle

Abstract

Store-operated Ca2+ entry (SOCE), mediated by the endoplasmic reticulum (ER) Ca2+ sensor stromal interaction molecule 1 (STIM1) and the plasma membrane (PM) channel Orai1, is inhibited during mitosis. STIM1 phosphorylation has been suggested to mediate this inhibition, but it is unclear whether additional pathways are involved. Here, we demonstrate using various approaches, including a nonphosphorylatable STIM1 knock-in mouse, that STIM1 phosphorylation is not required for SOCE inhibition in mitosis. Rather, multiple pathways converge to inhibit Ca2+ influx in mitosis. STIM1 interacts with the cochaperone BAG3 and localizes to autophagosomes in mitosis, and STIM1 protein levels are reduced. The density of ER-PM contact sites (CSs) is also dramatically reduced in mitosis, thus physically preventing STIM1 and Orai1 from interacting to activate SOCE. Our findings provide insights into ER-PM CS remodeling during mitosis and a mechanistic explanation of the inhibition of Ca2+ influx that is required for cell cycle progression.

Original languageEnglish
Pages (from-to)10392-10401
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number21
DOIs
Publication statusPublished - 1 Jan 2019

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Mitosis
Endoplasmic Reticulum
Phosphorylation
Cell Membrane
Stromal Interaction Molecule 1
Ion Channels
Cell Cycle
Proteins

Keywords

  • ER-PM contact sites
  • Mitosis
  • Mouse knock in
  • STIM1
  • Store-operated calcium entry

ASJC Scopus subject areas

  • General

Cite this

Remodeling of ER-plasma membrane contact sites but not STIM1 phosphorylation inhibits Ca2+ influx in mitosis. / Yu, Fang; Hubrack, Satanay Zuhair; Chakraborty, Sumita; Sun, Lu; Alcantara-Adap, Ethel; Kulkarni, Rashmi; Billing, Anja; Graumann, Johannes; Taylor, Colin W.; Machaca, Khaled.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 21, 01.01.2019, p. 10392-10401.

Research output: Contribution to journalArticle

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AU - Alcantara-Adap, Ethel

AU - Kulkarni, Rashmi

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