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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 6, 2004, 24(40):8862-8872; doi:10.1523/JNEUROSCI.3213-04.2004

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 ISI 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 ISI Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Vazquez, L. E. Articles by Kennedy, M. B. Search for Related Content PubMed PubMed Citation Articles by Vazquez, L. E. Articles by Kennedy, M. B. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene

 Previous Article  |  Next Article 

Cellular/Molecular
SynGAP Regulates Spine Formation

Luis E. Vazquez, Hong-Jung Chen, Irina Sokolova, Irene Knuesel, and Mary B. Kennedy

Division of Biology, California Institute of Technology, Pasadena, California 91125

SynGAP is a brain-specific ras GTPase-activating protein that is an abundant component of the signaling complex associated with the NMDA-type glutamate receptor. We generated mutant mice lacking synGAP to study its physiological role. Homozygous mutant mice die in the first few days after birth; however, neurons from mutant embryos can be maintained in culture. Here, we report that spine and synapse formation are accelerated in cultured mutant neurons, and the spines of mature mutant neurons are significantly larger than those of wild type. Clusters of PSD-95 and subunits of AMPA-type and NMDA-type glutamate receptors accumulate in spines of mutant neurons by day 10 in vitro, whereas in wild-type neurons they are still mostly located in dendritic shafts. The frequency and amplitude of miniature EPSCs are larger in mutant neurons at day 10 in vitro, confirming that they have more functional synapses. At day 21 in vitro, the spines of mutant neurons remain significantly larger than those of wild type. The mutant phenotype at day 10 in vitro can be rescued by introduction of recombinant wild-type synGAP on day 9. In contrast, introduction of mutant synGAP with a mutated GAP domain or lacking the terminal domain that binds to PSD-95 does not rescue the mutant phenotype, indicating that both domains play a role in control of spine formation. Thus, the GAP activity of synGAP and its association with PSD-95 are important for normal regulation of spine and synapse formation in hippocampal neurons.

Key words: synaptogenesis; postsynaptic; NMDA; AMPA; PSD-95; synapsin; filopodia; Ras

---

Received Feb 6, 2004; revised August 5, 2004; accepted August 24, 2004.

This article has been cited by other articles:

				C. D. Kopec, E. Real, H. W. Kessels, and R. Malinow GluR1 Links Structural and Functional Plasticity at Excitatory Synapses J. Neurosci., December 12, 2007; 27(50): 13706 - 13718. [Abstract] [Full Text] [PDF]

				M. J. Potthoff and E. N. Olson MEF2: a central regulator of diverse developmental programs Development, December 1, 2007; 134(23): 4131 - 4140. [Abstract] [Full Text] [PDF]

				Y.-L. Lin, Y.-T. Lei, C.-J. Hong, and Y.-P. Hsueh Syndecan-2 induces filopodia and dendritic spine formation via the neurofibromin-PKA-Ena/VASP pathway J. Cell Biol., June 21, 2007; 177(5): 829 - 841. [Abstract] [Full Text] [PDF]

				S. W. Flavell, C. W. Cowan, T.-K. Kim, P. L. Greer, Y. Lin, S. Paradis, E. C. Griffith, L. S. Hu, C. Chen, and M. E. Greenberg Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science, February 17, 2006; 311(5763): 1008 - 1012. [Abstract] [Full Text] [PDF]

				B. Calabrese, M. S. Wilson, and S. Halpain Development and Regulation of Dendritic Spine Synapses Physiology, February 1, 2006; 21(1): 38 - 47. [Abstract] [Full Text] [PDF]

				M. W. Barnett, R. F. Watson, T. Vitalis, K. Porter, N. H. Komiyama, P. N. Stoney, T. H. Gillingwater, S. G. N. Grant, and P. C. Kind Synaptic Ras GTPase Activating Protein Regulates Pattern Formation in the Trigeminal System of Mice J. Neurosci., February 1, 2006; 26(5): 1355 - 1365. [Abstract] [Full Text] [PDF]

				M. Nonaka, T. Doi, Y. Fujiyoshi, S. Takemoto-Kimura, and H. Bito Essential Contribution of the Ligand-Binding betaB/betaC Loop of PDZ1 and PDZ2 in the Regulation of Postsynaptic Clustering, Scaffolding, and Localization of Postsynaptic Density-95 J. Neurosci., January 18, 2006; 26(3): 763 - 774. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help