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Title
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Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.
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Authors
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E.Kim,
M.Niethammer,
A.Rothschild,
Y.N.Jan,
M.Sheng.
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Ref.
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Nature, 1995,
378,
85-88.
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PubMed id
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Abstract
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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.
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