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Title

ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain
Authors
Bulla, Monica
Gyimesi, G
Kim, J H
Bhardwaj, R
Hediger, M A
Frieden, Maud
Demaurex, Nicolas
Published in The Journal of Physiology. 2018
Abstract Gain-of-function mutations in the highly selective Ca2+ channel ORAI1 cause tubular aggregate myopathy (TAM) characterized by muscular pain, weakness and cramping. TAM-associated mutations in ORAI1 first and third transmembrane domain facilitate channel opening by STIM1, causing constitutive Ca2+ influx and increasing the currents evoked by Ca2+ store depletion. Mutation V107M additionally decreases the channel selectivity for Ca2+ ions and its inhibition by acidic pH, while mutation T184M does not alter the channel sensitivity to pH or to reactive oxygen species. The ORAI blocker GSK-7975A prevents the constitutive activity of TAM-associated channels and might be used in therapy for patients suffering from TAM.
Identifiers
PMID: 30382595
Full text
Article (Published version) (1.7 MB) - public document Free access
Other version: https://rdcu.be/bb8qf
Structures
Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Research group Signaux intracellulaires (210)
Projects FNS: 31003A‐149566
FNS: CRSII3‐16078
Citation
(ISO format) 		BULLA, Monica et al. ORAI1 channel gating and selectivity is differentially altered by natural mutations in the first or third transmembrane domain. In: The Journal of Physiology, 2018. https://archive-ouverte.unige.ch/unige:115764

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Deposited on : 2019-04-05

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