CLUSTERING OF SHAKER-TYPE K-ASSOCIATED GUANYLATE KINASES( CHANNELS BYINTERACTION WITH A FAMILY OF MEMBRANE)

ANCHORING Of ion channels at specific subcellular sites is critical fo r neuronal signalling, but the mechanisms underlying channel localizat ion and clustering are largely unknown (reviewed in ref. 1). Voltage-g ated K+ channels are concentrated in various neuronal domains, includi ng presynaptic terminals, nodes of Ranvier and dendrites, where they r egulate local membrane excitability. Here we present functional and bi ochemical evidence that cell-surface clustering of Shaker-subfamily K channels is mediated by the PSD-95 family of membrane-associated puta tive guanylate kinases, as a result of direct binding of the carboxy-t erminal cytoplasmic tails of the K+ channel subunits to two PDZ (also known as GLGF or DHR) domains in the PSD-95 protein(2). The ability of PDZ domains to function as independent modules for protein-protein in teraction, and their presence in other junction-associated molecules ( such as ZO-1 (ref. 3) and syntrophin(4)), suggest that PDZ-domain-cont aining polypeptides may be widely involved in the organization of prot eins at sites of membrane specialization.