Zusammenfassung
In many cells, increase in intracellular calcium ([Ca2+](i)) activates a Ca2+-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 ...
Zusammenfassung
In many cells, increase in intracellular calcium ([Ca2+](i)) activates a Ca2+-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-CF1'R, which is unable to exit the endoplasmic reticulum (ER). Since receptor-mediated [Ca2+](i) increase is Cl- dependent, we suggested that F508del-CFTR may function as an ER chloride counter-ion channel for Ca2+. This was confirmed by expression of the double mutant F508del/G551D-CFTR, which remained in the ER but had no effects on [Ca2+];. Moreover, F508del-CFTR could serve as a scavenger for inositol-1,4,5-trisphosphate [IP3] receptor binding protein released with IP3 (IRBIT). Our data may explain how ER-localized F508del-CFTR controls intracellular Ca2+ signaling. (C) 2011 Elsevier B.V. All rights reserved.
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