Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Different activation mechanisms of cystic fibrosis transmembrane conductance regulator expressed in Xenopus laevis oocytes
Autore:
Weber, WM; Segal, A; Vankeerberghen, A; Cassiman, JJ; Van Driessche, W;
Indirizzi:
Katholieke Univ Leuven, Physiol Lab, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 b, B-3000 Louvain, Belgium Katholieke Univ Leuven, Ctr Human Genet, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 t, B-3000 Louvain, Belgium
Titolo Testata:
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY
fascicolo: 3, volume: 130, anno: 2001,
pagine: 521 - 531
SICI:
1095-6433(200110)130:3<521:DAMOCF>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
ION CHANNELS; CL CHANNEL; CFTR; TRANSPORT; MEMBRANE; DISEASE; 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE; PRIMAQUINE; PROTEIN; CELLS;
Keywords:
adenosine triphosphate; brefeldin A; cyclic adenosine monophosphate; cystic fibrosis transmembrane conductance; regulator; exocytosis; heterologous expression; membrane capacitance; nocodazole; primaquine; protein trafficking;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Weber, WM Katholieke Univ Leuven, Physiol Lab, Campus Gasthuisberg, B-3000Louvain, Belgium Katholieke Univ Leuven Campus Gasthuisberg Louvain Belgium B-3000
Citazione:
W.M. Weber et al., "Different activation mechanisms of cystic fibrosis transmembrane conductance regulator expressed in Xenopus laevis oocytes", COMP BIOC A, 130(3), 2001, pp. 521-531

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP sensitive Cl- channel that is defective in cystic fibrosis (CF). The most frequent mutation, namely Delta F508-CFTR, accounts for 66% of CF. Here we show that cAMP-activation of CFTR occurs via at least two distinct pathways: activation of CFTR molecules already present in the plasma membrane and protein kinase A (PKA)-mediated vesicular transport of new CFTR molecules to the plasma membrane and functional insertion into the membrane. We investigated the mechanisms that are responsible for these activation pathways usingthe Xenopus laevis oocytes expression system. We expressed CFTR and recorded continuously membrane current (I-m), conductance (G(m)) and capacitance (C-m), which is a direct measure of membrane surface area. Expression of CFTR alone did not change the plasma membrane surface area. However, activation of CFTR with cAMP increased I-m, G(m) and C-m while Delta F508-CFTR-expressing oocytes showed no response on cAMP. Inhibition of protein kinase A or buffering intracellular Ca2+ abolished the cAMP-induced increase in C-m while increases of I-m and G(m) were still present. AT? or the xanthine derivative 8-cyclopentyl-1,3-dipropylxanthine (CPX) did not further activate CFTR. Insertion of pre-formed CFTR into the plasma membrane could be prevented by compounds that interfere with intracellular transport mechanisms such as primaquine, brefeldin A, nocodazole. From these data we conclude that cAMP activates CFTR by at least two distinct pathways: activation of CFTR already present in the plasma membrane and exocytotic delivery of new CFTR molecules to the oocyte membrane and functional insertion into it. (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/21 alle ore 02:48:09