A new K+ channel beta subunit to specifically enhance Kv2.2 (CDRK) expression.
Cloned K+ channel beta subunits are hydrophilic proteins which associate to pore-forming alpha subunits of the Shaker subfamily. The resulting alphabeta heteromultimers K+ channels have inactivation kinetics significantly more rapid than those of the corresponding alpha homomultimers. This paper reports the cloning and the brain localization of mKvbeta4 (m for mouse), a new beta subunit. This new beta subunit is highly expressed in the nervous system but is also present in other tissues such as kidney. In contrast with other beta subunits, coexpression of the mKvbeta4 subunit with alpha subunits of Shaker-type K+ channel does not modify the kinetic properties or voltage-dependence of these channels in Xenopus oocytes. Instead, mKvbeta4 associates to Kv2.2 (CDRK), a Shab K+ channel, to specifically enhance (a factor of up to 6) its expression level without changing its elementary conductance or kinetics. It is without effect on another closely related Shab K+ channel Kv2.1 (DRK1). Chimeras between Kv2.1 and Kv2. 2 indicate that the COOH-terminal end of the Kv2.2 protein is essential for its mKvbeta4 sensitivity. The functional results associated with the observation of the co-localization of mKvbeta4 and Kv2.2 transcripts in most brain areas strongly suggest that both subunits interact in vivo to form a slowly-inactivating K+ channel. A chaperone-like effect of mKvbeta4 seems to permit the integration of a larger number of Kv2.2 channels at the plasma membrane.
Fink
M
M
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660, route des Lucioles, Sophia Antipolis 06560 Valbonne, France.
Duprat
F
F
Lesage
F
F
Heurteaux
C
C
Romey
G
G
Barhanin
J
J
Lazdunski
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes; D015221:Potassium Channels / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014981:Xenopus
D018076:DNA, Complementary; D051668:Delayed Rectifier Potassium Channels; C496982:Kcna5 protein, mouse; C494838:Kcnab1 protein, mouse; C101877:Kcnab3 protein, mouse; C496990:Kcnb1 protein, mouse; C496993:Kcnb2 protein, mouse; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels