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- Title
TRIC-A shapes oscillatory Ca<sup>2+</sup> signals by interaction with STIM1/Orai1 complexes.
- Authors
Shrestha, Niroj; Bacsa, Bernadett; Ong, Hwei Ling; Scheruebel, Susanne; Bischof, Helmut; Malli, Roland; Ambudkar, Indu Suresh; Groschner, Klaus
- Abstract
Trimeric intracellular cation (TRIC) channels have been proposed to modulate Ca2+ release from the endoplasmic reticulum (ER) and determine oscillatory Ca2+ signals. Here, we report that TRIC-A–mediated amplitude and frequency modulation of ryanodine receptor 2 (RyR2)-mediated Ca2+ oscillations and inositol 1,4,5-triphosphate receptor (IP3R)-induced cytosolic signals is based on attenuating store-operated Ca2+ entry (SOCE). Further, TRIC-A–dependent delay in ER Ca2+ store refilling contributes to shaping the pattern of Ca2+ oscillations. Upon ER Ca2+ depletion, TRIC-A clusters with stromal interaction molecule 1 (STIM1) and Ca2+-release–activated Ca2+ channel 1 (Orai1) within ER–plasma membrane (PM) junctions and impairs assembly of the STIM1/Orai1 complex, causing a decrease in Orai1-mediated Ca2+ current and SOCE. Together, our findings demonstrate that TRIC-A is a negative regulator of STIM1/Orai1 function. Thus, aberrant SOCE could contribute to muscle disorders associated with loss of TRIC-A. Trimeric intracellular cation (TRIC) channels have been proposed to modulate calcium release from the endoplasmic reticulum (ER) and to determine oscillatory calcium signals. This study shows that upon depletion of ER calcium, TRIC-A coclusters and interferes with STIM1-Orai1 coupling within ER-plasma membrane junctions.
- Subjects
RYANODINE receptors; ENDOPLASMIC reticulum; AMPLITUDE modulation; CALCIUM channels; CALCIUM; OSCILLATIONS
- Publication
PLoS Biology, 2020, Vol 18, Issue 4, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.3000700