DOI: 10.1083/jcb.200211002. Synapse formation is regulated by the signaling adaptor GIT1

Synapse formation is regulated by the signaling adaptor GIT1

10.1083/jcb.200211002

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Dendritic spines in the central nervous system undergo rapid actin-based shape changes, making actin regulators potential modulators of spine morphology and synapse formation. Although several potential regulators and effectors for actin organization have been identified, the mechanisms by which these molecules assemble and localize are not understood. Here we show that the G protein–coupled receptor kinase–interacting protein (GIT)1 serves such a function by targeting actin regulators and locally modulating Rac activity at synapses. In cultured hippocampal neurons, GIT1 is enriched in both pre- and postsynaptic terminals and targeted to these sites by a novel domain. Disruption of the synaptic localization of GIT1 by a dominant-negative mutant results in numerous dendritic protrusions and a significant decrease in the number of synapses and normal mushroom-shaped spines. The phenotype results from mislocalized GIT1 and its binding partner PIX, an exchange factor for Rac. In addition, constitutively active Rac shows a phenotype similar to the GIT1 mutant, whereas dominant-negative Rac inhibits the dendritic protrusion formation induced by mislocalized GIT1. These results demonstrate a novel function for GIT1 as a key regulator of spine morphology and synapse formation and point to a potential mechanism by which mutations in Rho family signaling leads to decreased neuronal connectivity and cognitive defects in nonsyndromic mental retardation.

Bibliography

Zhang, H., Webb, D. J., Asmussen, H., & Horwitz, A. F. (2003). Synapse formation is regulated by the signaling adaptor GIT1. The Journal of Cell Biology, 161(1), 131â142.

Authors 4

Huaye Zhang (first)
Donna J. Webb (additional)
Hannelore Asmussen (additional)
Alan F. Horwitz (additional)

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Dates

Type	When
Created	22 years, 4 months ago (April 14, 2003, 2:18 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 10:13 a.m.)
Indexed	3 months, 1 week ago (May 17, 2025, 1:10 a.m.)
Issued	22 years, 4 months ago (April 14, 2003)
Published	22 years, 4 months ago (April 14, 2003)
Published Online	22 years, 4 months ago (April 14, 2003)
Published Print	22 years, 4 months ago (April 14, 2003)

Funders 0

None

BibTeX

@article{Zhang_2003, title={Synapse formation is regulated by the signaling adaptor GIT1}, volume={161}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200211002}, DOI={10.1083/jcb.200211002}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Zhang, Huaye and Webb, Donna J. and Asmussen, Hannelore and Horwitz, Alan F.}, year={2003}, month=apr, pages={131–142} }

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