Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.
ANCHORING of ion channels at specific subcellular sites is critical for neuronal signalling, but the mechanisms underlying channel localization and clustering are largely unknown (reviewed in ref. 1). Voltage-gated K+ channels are concentrated in various neuronal domains, including presynaptic terminals, nodes of Ranvier and dendrites, where they regulate local membrane excitability. Here we present functional and biochemical evidence that cell-surface clustering of Shaker-subfamily K+ channels is mediated by the PSD-95 family of membrane-associated putative guanylate kinases, as a result of direct binding of the carboxy-terminal cytoplasmic tails to the K+ channel subunits to two PDZ (also known as GLGF or DHR) domains in the PSD-95 protein. The ability of PDZ domains to function as independent modules for protein-protein interaction, and their presence in other junction-associated molecules (such as ZO-1 (ref. 3) and syntrophin), suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization.
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006168:Guinea Pigs; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051665:Kv1.4 Potassium Channel; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000074407:SAP90-PSD95 Associated Proteins; D012441:Saccharomyces cerevisiae; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; C501119:Dlg1 protein, rat; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C496977:KCNA4 protein, human; C496979:Kcna4 protein, rat; D051665:Kv1.4 Potassium Channel; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D000074407:SAP90-PSD95 Associated Proteins; D025521:Tumor Suppressor Proteins; C033652:postsynaptic density proteins; D009703:Nucleoside-Phosphate Kinase; C496468:DLG2 protein, human; D051528:Guanylate Kinases