QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (74) Citing Articles via Google Scholar Google Scholar Articles by Naisbitt, S. Articles by Sheng, M. Search for Related Content PubMed PubMed Citation Articles by Naisbitt, S. Articles by Sheng, M.

 Previous Article  |  Next Article 

Volume 17, Number 15, Issue of August 1, 1997 pp. 5687-5696
Copyright ©1997 Society for Neuroscience

Characterization of Guanylate Kinase-Associated Protein, a Postsynaptic Density Protein at Excitatory Synapses That Interacts Directly with Postsynaptic Density-95/Synapse-Associated Protein 90

Received March 17, 1997; revised May 12, 1997; accepted May 13, 1997.

Scott Naisbitt¹, Eunjoon Kim², Richard J. Weinberg³, Anuradha Rao⁴, Fu-Chia Yang¹, Ann Marie Craig⁴, and Morgan Sheng¹

¹ Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachussetts 02114, ² Department of Pharmacology, Pusan National University, Kumjeong-ku, Pusan 609-735, South Korea, ³ Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and ⁴ Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign, Illinois 61801

The structure of central synapses is poorly understood at the molecular level. A recent advance came with the identification of the postsynaptic density-95 (PSD-95)/synapse-associated protein 90 family of proteins as important mediators of the synaptic clustering of certain classes of ion channels. By yeast two-hybrid screening, a novel protein termed guanylate kinase-associated protein (GKAP) has been isolated that binds to the GK-like domain of PSD-95 (). Here we present a detailed characterization of GKAP expression in the rat brain and report the cloning of a novel GKAP splice variant. By Northern blot, GKAP mRNAs (4, 6.5, and 8 kB) are expressed predominantly in the rat brain. By in situ hybridization, GKAP is expressed widely in neurons of cortex and hippocampus and in the Purkinje and granule cells of the cerebellum. On brain immunoblots, two prominent bands of 95 and 130 kDa are detected that correspond to products of short and long N-terminal splice variants of GKAP. Two independent GKAP antibodies label somatodendritic puncta in neocortical and hippocampal neurons in a pattern consistent with synaptic elements. Immunogold electron microscopy reveals GKAP to be predominantly postsynaptic and present at asymmetric synapses and in dendritic spines. The distribution of GKAP immunogold particles is uniform in the lateral plane of the PSD but peaks in the perpendicular axis ~20 nm from the postsynaptic membrane. In cultured hippocampal neurons GKAP immunoreactive puncta colocalize with the AMPA receptor subunit Glu receptor 1 but not with the GABA_A receptor subunits 2 and 3. Thus GKAP is a widely expressed neuronal protein localized specifically in the PSD of glutamatergic synapses, consistent with its direct interaction with PSD-95 family proteins.

Key words: Postsynaptic density; excitatory synapse; PSD-95/SAP90; immunogold electron microscopy; glutamate receptor; guanylate kinase domain; MAGUK

This article has been cited by other articles:

				S. Romorini, G. Piccoli, M. Jiang, P. Grossano, N. Tonna, M. Passafaro, M. Zhang, and C. Sala A Functional Role of Postsynaptic Density-95-Guanylate Kinase-Associated Protein Complex in Regulating Shank Assembly and Stability to Synapses J. Neurosci., October 20, 2004; 24(42): 9391 - 9404. [Abstract] [Full Text] [PDF]

				M. J. Parker, S. Zhao, D. S. Bredt, J. R. Sanes, and G. Feng PSD93 Regulates Synaptic Stability at Neuronal Cholinergic Synapses J. Neurosci., January 14, 2004; 24(2): 378 - 388. [Abstract] [Full Text] [PDF]

				T. Okabe, T. Nakamura, Y. N. Nishimura, K. Kohu, S. Ohwada, Y. Morishita, and T. Akiyama RICS, a Novel GTPase-activating Protein for Cdc42 and Rac1, Is Involved in the beta -Catenin-N-cadherin and N-Methyl-D-aspartate Receptor Signaling J. Biol. Chem., March 7, 2003; 278(11): 9920 - 9927. [Abstract] [Full Text] [PDF]

				A. Yoshii, M. H. Sheng, and M. Constantine-Paton Eye opening induces a rapid dendritic localization of PSD-95 in central visual neurons PNAS, February 4, 2003; 100(3): 1334 - 1339. [Abstract] [Full Text] [PDF]

				I. Yao, J. Iida, W. Nishimura, and Y. Hata Synaptic and Nuclear Localization of Brain-Enriched Guanylate Kinase-Associated Protein J. Neurosci., July 1, 2002; 22(13): 5354 - 5364. [Abstract] [Full Text] [PDF]

				V. Heidinger, P. Manzerra, X. Q. Wang, U. Strasser, S.-P. Yu, D. W. Choi, and M. M. Behrens Metabotropic Glutamate Receptor 1-Induced Upregulation of NMDA Receptor Current: Mediation through the Pyk2/Src-Family Kinase Pathway in Cortical Neurons J. Neurosci., July 1, 2002; 22(13): 5452 - 5461. [Abstract] [Full Text] [PDF]

				S. Levi, R. M. Grady, M. D. Henry, K. P. Campbell, J. R. Sanes, and A. M. Craig Dystroglycan Is Selectively Associated with Inhibitory GABAergic Synapses But Is Dispensable for Their Differentiation J. Neurosci., June 1, 2002; 22(11): 4274 - 4285. [Abstract] [Full Text] [PDF]

				F. Imamura, S. Maeda, T. Doi, and Y. Fujiyoshi Ligand Binding of the Second PDZ Domain Regulates Clustering of PSD-95 with the Kv1.4 Potassium Channel J. Biol. Chem., January 25, 2002; 277(5): 3640 - 3646. [Abstract] [Full Text] [PDF]

				M. Sheng Molecular organization of the postsynaptic specialization PNAS, June 19, 2001; 98(13): 7058 - 7061. [Abstract] [Full Text] [PDF]

				S. Naisbitt, J. Valtschanoff, D. W. Allison, C. Sala, E. Kim, A. M. Craig, R. J. Weinberg, and M. Sheng Interaction of the Postsynaptic Density-95/Guanylate Kinase Domain-Associated Protein Complex with a Light Chain of Myosin-V and Dynein J. Neurosci., June 15, 2000; 20(12): 4524 - 4534. [Abstract] [Full Text] [PDF]

				R. S. Walikonis, O. N. Jensen, M. Mann, D. W. Provance Jr, J. A. Mercer, and M. B. Kennedy Identification of Proteins in the Postsynaptic Density Fraction by Mass Spectrometry J. Neurosci., June 1, 2000; 20(11): 4069 - 4080. [Abstract] [Full Text] [PDF]

				H. Shin, Y.-P. Hsueh, F.-C. Yang, E. Kim, and M. Sheng An Intramolecular Interaction between Src Homology 3 Domain and Guanylate Kinase-Like Domain Required for Channel Clustering by Postsynaptic Density-95/SAP90 J. Neurosci., May 15, 2000; 20(10): 3580 - 3587. [Abstract] [Full Text] [PDF]

				M Sheng and E Kim The Shank family of scaffold proteins J. Cell Sci., January 6, 2000; 113(11): 1851 - 1856. [Abstract] [PDF]

				R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis The Glutamate Receptor Ion Channels Pharmacol. Rev., March 1, 1999; 51(1): 7 - 62. [Abstract] [Full Text] [PDF]

				I. M. Ethell and Y. Yamaguchi Cell Surface Heparan Sulfate Proteoglycan Syndecan-2 Induces the Maturation of Dendritic Spines in Rat Hippocampal Neurons J. Cell Biol., February 8, 1999; 144(3): 575 - 586. [Abstract] [Full Text] [PDF]

				J. E. Brenman, J. R. Topinka, E. C. Cooper, A. W. McGee, J. Rosen, T. Milroy, H. J. Ralston, and D. S. Bredt Localization of Postsynaptic Density-93 to Dendritic Microtubules and Interaction with Microtubule-Associated Protein 1A J. Neurosci., November 1, 1998; 18(21): 8805 - 8813. [Abstract] [Full Text] [PDF]

				K. Hirao, Y. Hata, N. Ide, M. Takeuchi, M. Irie, I. Yao, M. Deguchi, A. Toyoda, T. C. Sudhof, and Y. Takai A Novel Multiple PDZ Domain-containing Molecule Interacting with N-Methyl-D-aspartate Receptors and Neuronal Cell Adhesion Proteins J. Biol. Chem., August 14, 1998; 273(33): 21105 - 21110. [Abstract] [Full Text] [PDF]

				Y.-P. Hsueh, F.-C. Yang, V. Kharazia, S. Naisbitt, A. R. Cohen, R. J. Weinberg, and M. Sheng Direct Interaction of CASK/LIN-2 and Syndecan Heparan Sulfate Proteoglycan and Their Overlapping Distribution in Neuronal Synapses J. Cell Biol., July 13, 1998; 142(1): 139 - 151. [Abstract] [Full Text] [PDF]

				A. Rao, E. Kim, M. Sheng, and A. M. Craig Heterogeneity in the Molecular Composition of Excitatory Postsynaptic Sites during Development of Hippocampal Neurons in Culture J. Neurosci., February 15, 1998; 18(4): 1217 - 1229. [Abstract] [Full Text] [PDF]

				M. Wyszynski, V. Kharazia, R. Shanghvi, A. Rao, A. H. Beggs, A. M. Craig, R. Weinberg, and M. Sheng Differential Regional Expression and Ultrastructural Localization of alpha -Actinin-2, a Putative NMDA Receptor-Anchoring Protein, in Rat Brain J. Neurosci., February 15, 1998; 18(4): 1383 - 1392. [Abstract] [Full Text] [PDF]

				H.-J. Kreienkamp, H. Zitzer, E. D. Gundelfinger, D. Richter, and T. M. Bockers The Calcium-independent Receptor for alpha -Latrotoxin from Human and Rodent Brains Interacts with Members of the ProSAP/SSTRIP/Shank Family of Multidomain Proteins J. Biol. Chem., October 13, 2000; 275(42): 32387 - 32390. [Abstract] [Full Text] [PDF]

				S. E. Craven and D. S. Bredt Synaptic Targeting of the Postsynaptic Density Protein PSD-95 Mediated by a Tyrosine-based Trafficking Signal J. Biol. Chem., June 23, 2000; 275(26): 20045 - 20051. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help