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Anchoring proteins confer G protein sensitivity to an inward‐rectifier K + channel through the GK domain
Author(s) -
Hibino Hiroshi,
Inanobe Atsushi,
Tanemoto Masayuki,
Fujita Akikazu,
Doi Katsumi,
Kubo Takeshi,
Hata Yutaka,
Takai Yoshimi,
Kurachi Yoshihisa
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.1.78
Subject(s) - biology , inward rectifier potassium ion channel , anchoring , sensitivity (control systems) , potassium channel , genetics , microbiology and biotechnology , biophysics , ion channel , receptor , structural engineering , electronic engineering , engineering
Anchoring proteins cluster receptors and ion channels at postsynaptic membranes in the brain. They also act as scaffolds for intracellular signaling molecules including synGAP and NO synthase. Here we report a new function for intracellular anchoring proteins: the regulation of synaptic ion channel function. A neuronal G protein‐gated inwardly rectifying K + channel, Kir3.2c, can not be activated either by M 2 ‐muscarinic receptor stimulation or by G βγ overexpression. When coexpressed with SAP97, a member of the PSD/SAP anchoring protein family, the channel became sensitive to G protein stimulation. Although the C‐terminus of Kir3.2c bound to the second PDZ domain of SAP97, functional analyses revealed that the guanylate kinase (GK) domain of SAP97 is crucial for sensitization of the Kir3.2c channel to G protein stimulation. Furthermore, SAPAP1/GKAP, which binds specifically to the GK domain of membrane‐associated guanylate kinases, prevented the SAP97‐induced sensitization. The function of a synaptic ion channel can therefore be controlled by a network of various intracellular proteins.