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Sci Rep. 2019 Jul 25;9(1):10839. doi: 10.1038/s41598-019-46862-w.

Septins organize endoplasmic reticulum-plasma membrane junctions for STIM1-ORAI1 calcium signalling.

Author information

1
Division of Signalling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
2
NOMIS Center for Immunobiology and Microbial Pathogenesis & Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
3
Translational Science Division, Clinical Science Department, Moffitt Cancer Center Magnolia Campus, Tampa, FL, 33612, USA.
4
NOMIS Center for Immunobiology and Microbial Pathogenesis & Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA. blillemeier@salk.edu.
5
Division of Signalling and Gene Expression, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA. phogan@lji.org.
6
Program in Immunology, University of California San Diego, La Jolla, CA, 92037, USA. phogan@lji.org.
7
Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA. phogan@lji.org.

Abstract

ORAI1 Ca2+ channels in the plasma membrane (PM) are gated by STIM1 at endoplasmic reticulum (ER)-PM junctions to effect store-dependent Ca2+ entry into cells, but little is known about how local STIM-ORAI signalling at junctions is coordinated with overall cellular architecture. Filamentous septins can specify cytoskeletal rearrangements and have been found recently to modulate STIM-ORAI signalling. Here we show by super-resolution imaging of ORAI1, STIM1, and septin 4 in living cells that septins facilitate Ca2+ signalling indirectly. Septin 4 does not colocalize preferentially with ORAI1 in resting or stimulated cells, assemble stably at ER-PM junctions, or specify a boundary that directs or confines ORAI1 to junctions. Rather, ORAI1 is recruited to junctions solely through interaction with STIM proteins, while septins regulate the number of ER-PM junctions and enhance STIM1-ORAI1 interactions within junctions. Thus septins communicate with STIM1 and ORAI1 through protein or lipid intermediaries, and are favorably positioned to coordinate Ca2+ signalling with rearrangements in cellular architecture.

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