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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind116
Udgave nummer21
Sider (fra-til)10392-10401
Antal sider10
ISSN0027-8424
DOI
StatusUdgivet - 10. dec. 2019
Udgivet eksterntJa

Fingeraftryk Dyk ned i forskningsemnerne om 'Remodeling of ER-plasma membrane contact sites but not STIM1 phosphorylation inhibits Ca<sup>2+</sup> influx in mitosis'. Sammen danner de et unikt fingeraftryk.

Citationsformater