PSD-95 mediates formation of a functional homomeric Kir5.1 channel in the brain.
Homomeric assembly of Kir5.1, an inward-rectifying K+ channel subunit, is believed to be nonfunctional, although the subunit exists abundantly in the brain. We show that HEK293T cells cotransfected with Kir5.1 and PSD-95 exhibit a Ba(2+)-sensitive inward-rectifying K+ current. Kir5.1 coexpressed with PSD-95 located on the plasma membrane in a clustered manner, while the Kir5.1 subunit expressed alone distributed mostly in cytoplasm, probably due to rapid internalization. The binding of Kir5.1 with PSD-95 was prevented by protein kinase A (PKA)-mediated phosphorylation of its carboxyl terminus. The currents flowing through Kir5.1/PSD-95 were suppressed promptly and reversibly by PKA activation. Because the Kir5.1/PSD-95 complex was detected in the brain, this functional brain K+ channel is potentially a novel physiological target of PKA-mediated signaling.
Tanemoto
Masayuki
M
Department of Pharmacology II, Graduate School of Medicine A7, Osaka University, Yamada-oka 2-2, Suita, Osaka 565-0871, Japan.
Fujita
Akikazu
A
Higashi
Kayoko
K
Kurachi
Yoshihisa
Y
D000818:Animals; D001464:Barium / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002458:Cell Fractionation; D002460:Cell Line; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins; C033652:postsynaptic density proteins; D001464:Barium; D017868:Cyclic AMP-Dependent Protein Kinases