ARF6-dependent interaction of the TWIK1 K+ channel with EFA6, a GDP/GTP exchange factor for ARF6.
TWIK1 belongs to a family of K(+) channels involved in neuronal excitability and cell volume regulation. Its tissue distribution suggests a role in epithelial potassium transport. Here we show that TWIK1 is expressed in a subapical compartment in renal proximal tubules and in polarized MDCK cells. In nonpolarized cells, this compartment corresponds to pericentriolar recycling endosomes. We identified EFA6, an exchange factor for the small G protein ADP-ribosylation factor 6 (ARF6), as a protein binding to TWIK1. EFA6 interacts with TWIK1 only when it is bound to ARF6. Because ARF6 modulates endocytosis at the apical surface of epithelial cells, the ARF6/EFA6/TWIK1 association is probably important for channel internalization and recycling.
Decressac
Sonia
S
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR6097/UNSA, Institut Paul Hamel, 660, route des lucioles, 06560 Valbonne, France.
Franco
Michel
M
Bendahhou
Said
S
Warth
Richard
R
Knauer
Sebastian
S
Barhanin
Jacques
J
Lazdunski
Michel
M
Lesage
Florian
F
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D004705:Endocytosis / Q000502:physiology; D005455:Fluorescent Antibody Technique; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins; D010445:Peptide Elongation Factors / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D000089982:ADP-Ribosylation Factor 6; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; C109970:PSD protein, human; D010445:Peptide Elongation Factors; D015221:Potassium Channels; C504474:Psd protein, mouse; D014168:Transferrin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse