GKAP, a Novel Synaptic Protein That Interacts with the Guanylate Kinase-like Domain of the PSD-95/SAP90 Family of Channel Clustering Molecules

다국어 초록 (Multilingual Abstract)

The molecular mechanisms underlying the organization of ion channels and signsling molecules at the synaptic junction are largely unknown. Recently, members of the PSD-95/SAP90 family of synaptic MAGUK(menbrane-acssociated guanylate kinase) proteins have been shown to interact. via their NH_2-terminal PDZ domains, with certain ion channels(NMDA receptors and K^+channels). thereby promoting the clustering of these proteins. Although the function of the NH_2-terminal PDZ domains in relatively well characterized, the function of the Src homology 3(SH3) domain and the guanylate kinase-like(GK)domain in the COOH-terminal half of PSD-95 has remained obscure. WE now repoet the isolation of a novel synaptic protein. termed GKAP for guanylate kinase-associated protein. that binds directly to the GK domain of the known members of the mammalian PSD-95 family. GKAP shows a unique domain structure and appear to be a major constituent of the postsynaptic density. GKAP colocalizes and coimmunoprecipitates with PSD-95 in vivo,and colusters with PSD-95 and K^+ channels/parent lack of guanylate kinase enzymatic activity, the fact that the GK domain can as a site for protein-protein interaction has implications for the function of diverse GK-containing proteins(such as p55,ZO-1,and LIN-2/CASK).