Biochim Biophys Acta 2011 Nov 01;181211:1385-92. doi: 10.1016/j.bbadis.2011.08.008.

F508del-CFTR increases intracellular Ca(2+) signaling that causes enhanced calcium-dependent Cl(-) conductance in cystic fibrosis.

???displayArticle.abstract???
In many cells, increase in intracellular calcium ([Ca(2+)](i)) activates a Ca(2+)-dependent chloride (Cl(-)) conductance (CaCC). CaCC is enhanced in cystic fibrosis (CF) epithelial cells lacking Cl(-) transport by the CF transmembrane conductance regulator (CFTR). Here, we show that in freshly isolated nasal epithelial cells of F508del-homozygous CF patients, expression of TMEM16A and bestrophin 1 was unchanged. However, calcium signaling was strongly enhanced after induction of expression of F508del-CFTR, which is unable to exit the endoplasmic reticulum (ER). Since receptor-mediated [Ca(2+)](i) increase is Cl(-) dependent, we suggested that F508del-CFTR may function as an ER chloride counter-ion channel for Ca(2+). This was confirmed by expression of the double mutant F508del/G551D-CFTR, which remained in the ER but had no effects on [Ca(2+)](i). Moreover, F508del-CFTR could serve as a scavenger for inositol-1,4,5-trisphosphate [IP3] receptor binding protein released with IP(3) (IRBIT). Our data may explain how ER-localized F508del-CFTR controls intracellular Ca(2+) signaling.

???displayArticle.pubmedLink??? 21907281
???displayArticle.link??? Biochim Biophys Acta


Species referenced: Xenopus laevis
Genes referenced: ahcyl1 ano1 cftr clca1.3
GO keywords: intracellular calcium activated chloride channel activity [+]

???displayArticle.disOnts??? cystic fibrosis
???displayArticle.omims??? CYSTIC FIBROSIS; CF