Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Leucine-rich repeat-containing 8 (LRRC8) proteins have been proposed to evolutionarily originate from the combination of the channel protein pannexin, and a leucine-rich repeat (LRR) domain. Five paralogs of LRRC8, namely LRRC8A,
LRRC8B
, LRRC8C, LRRC8D and LRRC8E have been reported. LRRC8A has been shown to be instrumental in cell swelling. Here, we identify
LRRC8B
as a key player in the cellular Ca
2+
signaling network. Overexpression of human
LRRC8B
in HEK293 cells reduced the Ca
2+
level in the endoplasmic reticulum (ER).
LRRC8B
-overexpressing cells exhibited a lesser release of Ca
2+
from the ER in response to ATP, carbachol and intracellular administration of inositol (1,4,5)-trisphosphate (IP
3
).
LRRC8B
-knockdown cells showed a slower depletion of the ER Ca
2+
stores when sarco-endoplasmic reticulum Ca
2+
-
ATPase
was blocked with thapsigargin (TG), while overexpression of
LRRC8B
had the opposite effect.
LRRC8B
-overexpressing cells exhibited a higher level of store-operated Ca
2+
entry following store-depletion by TG. Collectively,
LRRC8B
participates in intracellular Ca
2+
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 Ca
2+
leak and expands the known roles for LRRC8 proteins.This article has an associated First Person interview with the first author of the paper.
...
PMID:Leucine-rich repeat-containing 8B protein is associated with the endoplasmic reticulum Ca
2+
leak in HEK293 cells. 2930 42
