MUTANT (DELTA-F508) CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR CL- CHANNEL IS FUNCTIONAL WHEN RETAINED IN ENDOPLASMIC-RETICULUM OFMAMMALIAN-CELLS

Citation
Ea. Pasyk et Jk. Foskett, MUTANT (DELTA-F508) CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR CL- CHANNEL IS FUNCTIONAL WHEN RETAINED IN ENDOPLASMIC-RETICULUM OFMAMMALIAN-CELLS, The Journal of biological chemistry, 270(21), 1995, pp. 12347-12350
Citations number
39
Language
INGLESE
art.tipo
Note
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
270
Issue
21
Year of publication
1995
Pages
12347 - 12350
Database
ISI
SICI code
0021-9258(1995)270:21<12347:M(CTCR>2.0.ZU;2-R
Abstract
Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a plasma membran e-localized chloride channel, Some mutations in CFTR, including one wh ich affects most patients (Delta F508-CFTR), prevent CFTR from exiting the endoplasmic reticulum (ER) where it is synthesized. To examine wh ether normal and mutant CFTRs function as chloride channels when they reside in the ER, the patch clamp technique was used to measure curren ts in the outer membrane of nuclei isolated from mammalian cells expre ssing CFTR. Both Delta F508-CFTR as well as CFTR were revealed to func tion as cAMP-regulated chloride channels in native ER membrane. These results represent the first demonstrations of functional activity of C FTR in the biosynthetic pathway and suggest that conformational change s in the mutant protein, although recognized by ER-retention mechanism s, do not necessarily affect CFTR chloride channel properties, which m ay have implications for pathophysiology and therapeutic interventions in cystic fibrosis.