STIM1, an essential and conserved component of store-operated Ca2 <b>+</b> channel function

2005/05/02 by Jack Roos, Paul J. DiGregorio, Andriy V. Yeromin +11 · 33 citations
Neuroscience · Biochemistry, Genetics and Molecular Biology · Medicine · #Ion Channels and Receptors #Ion channel regulation and function #Respiratory and Cough-Related Research

paper · pdf · doi:10.1083/jcb.200502019

Abstract

Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca2+ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca2+ entry. Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca2+ release-activated Ca2+ (CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity in Jurkat T cells. RNAi-mediated knockdown of STIM1 inhibited TG- or agonist-dependent Ca2+ entry in HEK293 or SH-SY5Y cells. Conversely, overexpression of STIM1 in HEK293 cells modestly enhanced TG-induced Ca2+ entry. We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels.

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• STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. [europepmc]
• STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. [europepmc]
• CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. [europepmc]
• Amplification of CRAC current by STIM1 and CRACM1 (Orai1). [europepmc]
• Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1. [europepmc]
• Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. [europepmc]
• CRACM1 multimers form the ion-selective pore of the CRAC channel. [europepmc]
• STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. [europepmc]
• Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. [europepmc]
• New developments in mast cell biology. [europepmc]
• T cell activation. [europepmc]
• SOAR and the polybasic STIM1 domains gate and regulate Orai channels. [europepmc]
• STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. [europepmc]
• STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. [europepmc]
• The functional network of ion channels in T lymphocytes. [europepmc]
• Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. [europepmc]
• Signalling ballet in space and time. [europepmc]
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• Crystal structure of the calcium release-activated calcium channel Orai. [europepmc]
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• The endoplasmic reticulum: structure, function and response to cellular signaling. [europepmc]
• Intracellular Ca 2+ Sensing: Its Role in Calcium Homeostasis and Signaling. [europepmc]
• Here, there, and everywhere: The importance of ER membrane contact sites. [europepmc]
• Calcium signalling in T cells. [europepmc]

Related

• STIM1L is a new actin-binding splice variant involved in fast repetitive Ca2+ release
• Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels
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