Open AccessLeucine-rich repeat-containing 8B (LRRC8B) protein is associated with the endoplasmic reticulum calcium leak in HEK293 cells
Author(s) -
Arijita Ghosh,
Nitin Khandelwal,
Arvind Kumar,
Amal Kanti Bera
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.203646
Subject(s) - biology , endoplasmic reticulum , leak , stim1 , microbiology and biotechnology , calcium , leucine , hek 293 cells , biochemistry , gene , medicine , amino acid , environmental engineering , engineering
Leucine-rich repeat-containing 8 (LRRC8) proteins have been proposed to be originated from the combination of a channel protein pannexin, and a leucine-rich repeat (LRR) domain. Five paralogs of LRRC8, namely LRRC8A, B, C, D and E have been reported. LRRC8A has been shown to be instrumental in cell swelling. We have identified LRRC8B as a key player in cellular Ca2+ signaling network. Overexpression of human LRRC8B in HEK293 cells reduced Ca2+ level in the endoplasmic reticulum (ER). LRRC8B overexpressed cells exhibited lesser release of ER-Ca2+ in response to ATP, carbachol and intracellular administration of IP3. LRRC8B knockdown cells showed slower depletion of the ER-Ca2+ stores when sarco-endoplasmic reticulum Ca2+-ATPase was blocked with thapsigargin (TG), while overexpression of LRRC8B had opposite effect. LRRC8B overexpressed cells exhibited a higher level of store-operated Ca2+ entry following store-depletion by TG. Collectively, LRRC8B participates in intracellular Ca2+ homeostasis by acting as a leak channel in the ER. This study gives a fundamental understanding of the role of a novel protein in the elemental cellular process of ER-Ca2+ leak and paves new dimensions for LRRC8 proteins.