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Scientific article
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English

Enforced tethering elongates the cortical endoplasmic reticulum and limits store-operated calcium entry

Contributors

Henry, Christopher; Carreras Sureda, Amado; Demaurex, Nicolas

Published in

Journal of cell science

Publication date

2022-02-22

First online date

2022-02-22

Abstract

Recruitment of STIM proteins to cortical ER (cER) domains forming membrane contact sites (MCS) mediate the store-operated Ca2+ entry (SOCE) pathway essential for human immunity. The cER is dynamically regulated by STIM and tethering proteins during SOCE, but the ultrastructural rearrangement and functional consequences of cER remodelling are unknown. Here, we express natural (E-Syt1/2) and artificial (MAPPER-S/L) protein tethers in HEK-293T cells and correlate the changes in cER length and gap distance measured by electron microscopy with ionic fluxes. Native cER cisternae extended during store depletion and remained elongated at constant ER-PM gap distance during subsequent Ca2+ elevations. Tethering proteins enhanced store-dependent cER expansion, anchoring the enlarged cER at tether-specific gap distances of 12-15nm (E-Syts) and 5-9nm (MAPPERs). Cells with artificially extended cER had reduced SOCE and reduced agonist-induced Ca2+ release. SOCE remained modulated by calmodulin and exhibited enhanced Ca2+-dependent inhibition. We propose that cER expansion mediated by ER-PM tethering at a close distance negatively regulates SOCE by confining STIM-ORAI complexes to the periphery of enlarged cER sheets, a process that might participate in the termination of store-operated Ca2+ entry.

Keywords

  • Calcium signaling
  • Electron microscopy
  • Innate immunity
  • Ion channels
  • Membrane contact sites
  • Muscle physiology

UNIGE affiliation entities

UNIGE research groups

Funding

Citation (ISO format)

HENRY, Christopher, CARRERAS SUREDA, Amado, DEMAUREX, Nicolas. Enforced tethering elongates the cortical endoplasmic reticulum and limits store-operated calcium entry. In: Journal of cell science, 2022. doi: 10.1242/jcs.259313

Main files (1)

Article (Accepted version)
CC BY

Identifiers

Journal ISSN

0021-9533
324views
226downloads

Technical informations

Creation

07/03/2022 12:14:00

First validation

07/03/2022 12:14:00

Update

16/03/2023 02:50:32

Status update

16/03/2023 02:50:31

Last indexation

01/11/2024 01:07:12
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