Dominant negative chimeras provide evidence for homo and heteromultimeric assembly of inward rectifier K+ channel proteins via their N-terminal end.
Chimeras have been constructed using three different fragments (N-terminal, central and C-terminal) of IRK3, a constitutive inward rectifier K+ channel subunit, and GIRK2, a G-protein activated inward rectifier K+ channel subunit and have been coinjected into Xenopus oocytes together with IRK3 or IRK1 (another constitutive inward rectifier) cRNA. Both IRK1 and IRK3 expression was inhibited by coinjection with chimeras containing a N-terminal fragment of IRK3 suggesting that subunits of K+ channels in the IRK family form a functional multimeric assembly where the N-terminal end has an important role. In situ hybridization shows that IRK1 and IRK3 are coexpressed in the same areas of the brain and probably in the same cells. Taken together both the localization and the oocyte expression results suggest that not only homomultimeric IRK1 or homomultimeric IRK3 assemblies take place but that heteromultimeric IRK1/IRK3 assemblies are also formed.
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Valbonne, France.
M
M
Fink
F
F
Duprat
C
C
Heurteaux
F
F
Lesage
G
G
Romey
J
J
Barhanin
M
M
Lazdunski
D000818:Animals; D001923:Brain Chemistry; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D017403:In Situ Hybridization; D046911:Macromolecular Substances; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins; D014018:Tissue Distribution; D014981:Xenopus
D046911:Macromolecular Substances; D010446:Peptide Fragments; D015221:Potassium Channels; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins