Unknown

Dataset Information

0

Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3.


ABSTRACT: We evaluated currents induced by expression of human homologs of Orai together with STIM1 in human embryonic kidney cells. When co-expressed with STIM1, Orai1 induced a large inwardly rectifying Ca(2+)-selective current with Ca(2+)-induced slow inactivation. A point mutation of Orai1 (E106D) altered the ion selectivity of the induced Ca(2+) release-activated Ca(2+) (CRAC)-like current while retaining an inwardly rectifying I-V characteristic. Expression of the C-terminal portion of STIM1 with Orai1 was sufficient to generate CRAC current without store depletion. 2-APB activated a large relatively nonselective current in STIM1 and Orai3 co-expressing cells. 2-APB also induced Ca(2+) influx in Orai3-expressing cells without store depletion or co-expression of STIM1. The Orai3 current induced by 2-APB exhibited outward rectification and an inward component representing a mixed calcium and monovalent current. A pore mutant of Orai3 inhibited store-operated Ca(2+) entry and did not carry significant current in response to either store depletion or addition of 2-APB. Analysis of a series of Orai1-3 chimeras revealed the structural determinant responsible for 2-APB-induced current within the sequence from the second to third transmembrane segment of Orai3. The Orai3 current induced by 2-APB may reflect a store-independent mode of CRAC channel activation that opens a relatively nonselective cation pore.

SUBMITTER: Zhang SL 

PROVIDER: S-EPMC2427323 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3.

Zhang Shenyuan L SL   Kozak J Ashot JA   Jiang Weihua W   Yeromin Andriy V AV   Chen Jing J   Yu Ying Y   Penna Aubin A   Shen Wei W   Chi Victor V   Cahalan Michael D MD  

The Journal of biological chemistry 20080417 25


We evaluated currents induced by expression of human homologs of Orai together with STIM1 in human embryonic kidney cells. When co-expressed with STIM1, Orai1 induced a large inwardly rectifying Ca(2+)-selective current with Ca(2+)-induced slow inactivation. A point mutation of Orai1 (E106D) altered the ion selectivity of the induced Ca(2+) release-activated Ca(2+) (CRAC)-like current while retaining an inwardly rectifying I-V characteristic. Expression of the C-terminal portion of STIM1 with Or  ...[more]

Similar Datasets

| S-EPMC2780800 | biostudies-literature
| S-EPMC3186358 | biostudies-literature
| S-EPMC3696057 | biostudies-literature
| S-EPMC2885196 | biostudies-literature
| S-EPMC2919135 | biostudies-literature
| S-EPMC4621783 | biostudies-literature
| S-EPMC3658112 | biostudies-literature
| S-EPMC3309402 | biostudies-literature
| S-EPMC2757196 | biostudies-literature
| S-EPMC3512576 | biostudies-literature