Editors' ChoiceNeurobiology

Anchoring G Protein to K+ Channel Kir3.2c

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Science's STKE  25 Jan 2000:
Vol. 2000, Issue 16, pp. tw2
DOI: 10.1126/stke.2000.16.tw2

Specific location and local concentration of receptors on the plasma membrane surface can be of the utmost importance for successful signaling. This is particularly true at the neural synapse where many signals may have to be transmitted in order to overcome a signaling threshold. Anchoring proteins have a crucial role in the placement and clustering of channels in postsynaptic membranes. Additionally, they serve as cytoplasmic docking sites for signaling proteins. Now a new function of anchoring proteins has been identified. Hibino et al. demonstrate the ability of the anchoring protein SAP97 to sensitize an inward-rectifier K+ channel, Kir3.2c, to G proteins. Xenopus oocytes injected with Kir3.2c alone followed by muscarinic receptor activation or overexpression of Gβγ could not activate Kir3.2c. However, coexpression of Kir3.2c and SAP97 allowed strong activation of Kir3.2c under the same conditions. SAP97 is composed of three PDZ domains, followed by an SH3 domain and a catalytically inactive guanylate kinase (GK) domain proximal to the COOH terminus. While the second PDZ domain of SAP97 is shown to bind the COOH terminus of Kir3.2c, the inactive GK domain is crucial for conferring G protein sensitivity to Kir3.2c channels. Coexpression of SAPAP1, a protein that binds the GK domain of SAP97, completely blocked the ability of SAP97 to sensitize Kir3.2c. Under the experimental conditions used, Hibino et al. were unable to demonstrate a direct association of muscarinic receptors, Gα or Gβγ with SAP97. Nonetheless, these observations reveal a possible role for anchoring proteins to couple ion channels and G proteins, and raise the possibility that competition for binding to the GK domain of SAP97 could influence such coupling.

Hibino, H., Inanobe, A., Tanemoto, M., Fujita, A., Doi, K., Kubo, T., Hata, Y., Takai, Y., and Kurachi, Y. (2000). Anchoring proteins confer G protein sensitivity to an inward-rectifier K+ channel through the GK domain. EMBO J. 19: 78 -83. [Abstract] [Full Text]

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