CLCA2 is a positive regulator of store-operated calcium entry and TMEM16A | Zendy

Aarushi Sharma | Zendy; Grace Ramena | Zendy; Yufang Yin | Zendy; Louis S. Premkumar | Zendy; Randolph C. Elble | Zendy

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CLCA2 is a positive regulator of store-operated calcium entry and TMEM16A

Author(s) -

Aarushi Sharma,

Grace Ramena,

Yufang Yin,

Louis S. Premkumar,

Randolph C. Elble

Publication year - 2018

Publication title -

plos one

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.99

H-Index - 332

ISSN - 1932-6203

DOI - 10.1371/journal.pone.0196512

Subject(s) - chloride channel , calcium , calcium in biology , microbiology and biotechnology , hek 293 cells , intracellular , chemistry , cytosol , voltage dependent calcium channel , regulator , calcium channel , immunoprecipitation , t type calcium channel , biophysics , biochemistry , biology , receptor , gene , organic chemistry , enzyme

The Chloride Channel Accessory (CLCA) protein family was first characterized as regulators of calcium-activated chloride channel (CaCC) currents (I CaCC ), but the mechanism has not been fully established. We hypothesized that CLCAs might regulate I CaCC by modulating intracellular calcium levels. In cells stably expressing human CLCA2 or vector, we found by calcium imaging that CLCA2 moderately enhanced intracellular-store release but dramatically increased store-operated entry of calcium upon cytosolic depletion. Moreover, another family member, CLCA1, produced similar effects on intracellular calcium mobilization. Co-immunoprecipitation revealed that CLCA2 interacted with the plasma membrane store-operated calcium channel ORAI-1 and the ER calcium sensor STIM-1. The effect of CLCA2 on I CaCC was tested in HEK293 stably expressing calcium-activated chloride channel TMEM16A. Co-expression of CLCA2 nearly doubled I CaCC in response to a calcium ionophore. These results unveil a new mechanism by which CLCA family members activate I CaCC and suggest a broader role in calcium-dependent processes.

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