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SHR Neuro Krebs Kardio Lipid

Butorac, C; Muik, M; Derler, I; Stadlbauer, M; Lunz, V; Krizova, A; Lindinger, S; Schober, R; Frischauf, I; Bhardwaj, R; Hediger, MA; Groschner, K; Romanin, C.
A novel STIM1-Orai1 gating interface essential for CRAC channel activation
CELL CALCIUM. 2019; 79: 57-67. [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Groschner Klaus
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Abstract:
Calcium signalling through store-operated calcium (SOC) entry is of crucial importance for T-cell activation and the adaptive immune response. This entry occurs via the prototypic Ca2+ release-activated Ca2+ (CRAC) channel. STIM1, a key molecular component of this process, is located in the membrane of the endoplasmic reticulum (ER) and is initially activated upon Ca2+ store depletion. This activation signal is transmitted to the plasma membrane via a direct physical interaction that takes place between STIM1 and the highly Ca2+-selective ion channel Orai1. The activation of STIM1 induces an extended cytosolic conformation. This, in turn, exposes the CAD/SOAR domain and leads to the formation of STIM1 oligomers. In this study, we focused on a small helical segment (STIM1 alpha 3, aa 400-403), which is located within the CAD/SOAR domain. We determined this segment's specific functional role in terms of STIM1 activation and Orai1 gating. The STIM1 alpha 3 domain appears not essential for STIM1 to interact with Orai1. Instead, it represents a key domain that conveys STIM1 interaction into Orai1 channel gating. The results of cysteine crosslinking experiments revealed the close proximity of STIM1 alpha 3 to a region within Orai1, which was located at the cytosolic extension of transmembrane helix 3, forming a STIM1-Orai1 gating interface (SOGI). We suggest that the interplay between STIM1 alpha 3 and Orai1 TM3 allows STIM1 coupling to be transmitted into physiological CRAC channel activation.

Find related publications in this database (Keywords)
STIM1
Orai1
CRAC channel gating
Patch-clamp
Fluorescence microscopy
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