Abstract
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 cyto-plasmic tails of the K+ channel subunits to two PDZ (also known as GLGF or DHR) domains in the PSD-95 protein2. 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 syntrophin4), suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization.
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Kim, E., Niethammer, M., Rothschild, A. et al. Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature 378, 85–88 (1995). https://doi.org/10.1038/378085a0
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DOI: https://doi.org/10.1038/378085a0
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