Targeting the PDZ Domains of Molecular Scaffolds of Transmembrane Ion Channels

Targeting the PDZ domains of molecular scaffolds of transmembrane ion channels

The AAPS Journal ◽

10.1007/bf02854911 ◽

2006 ◽

Vol 8 (2) ◽

pp. E396-E401 ◽

Cited By ~ 8

Author(s):

Andrea Piserchio ◽

Mark Spaller ◽

Dale F. Mierke

Keyword(s):

Ion Channels ◽

Pdz Domains ◽

Molecular Scaffolds

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

The Journal of Cell Biology ◽

10.1083/jcb.136.3.669 ◽

1997 ◽

Vol 136 (3) ◽

pp. 669-678 ◽

Cited By ~ 333

Author(s):

Eunjoon Kim ◽

Scott Naisbitt ◽

Yi-Ping Hsueh ◽

Anuradha Rao ◽

Adam Rothschild ◽

...

Keyword(s):

Ion Channels ◽

Nmda Receptors ◽

Molecular Mechanisms ◽

Major Constituent ◽

Synaptic Protein ◽

Pdz Domains ◽

Guanylate Kinase ◽

Apparent Lack ◽

K Channels

The molecular mechanisms underlying the organization of ion channels and signaling molecules at the synaptic junction are largely unknown. Recently, members of the PSD-95/SAP90 family of synaptic MAGUK (membrane-associated guanylate kinase) proteins have been shown to interact, via their NH2-terminal PDZ domains, with certain ion channels (NMDA receptors and K+ channels), thereby promoting the clustering of these proteins. Although the function of the NH2-terminal PDZ domains is 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 report the isolation of a novel synaptic protein, termed GKAP for guanylate kinase-associated protein, that binds directly to the GK domain of the four known members of the mammalian PSD-95 family. GKAP shows a unique domain structure and appears to be a major constituent of the postsynaptic density. GKAP colocalizes and coimmunoprecipitates with PSD-95 in vivo, and coclusters with PSD-95 and K+ channels/ NMDA receptors in heterologous cells. Given their apparent lack of guanylate kinase enzymatic activity, the fact that the GK domain can act 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).

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