Synapse formation is regulated by the signaling adaptor GIT1

Huaye Zhang, Donna J. Webb, Hannelore Asmussen, Alan F. Horwitz

Research output: Contribution to journalArticle

143 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)131-142
Number of pages12
JournalJournal of Cell Biology
Volume161
Issue number1
DOIs
StatePublished - Apr 14 2003
Externally publishedYes

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Synapses
Actins
Spine
G-Protein-Coupled Receptor Kinases
Receptor-Interacting Protein Serine-Threonine Kinases
Phenotype
Dendritic Spines
Agaricales
Presynaptic Terminals
Intellectual Disability
Central Nervous System
Neurons
Mutation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Zhang, Huaye ; Webb, Donna J. ; Asmussen, Hannelore ; Horwitz, Alan F. / Synapse formation is regulated by the signaling adaptor GIT1. In: Journal of Cell Biology. 2003 ; Vol. 161, No. 1. pp. 131-142.
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Synapse formation is regulated by the signaling adaptor GIT1. / Zhang, Huaye; Webb, Donna J.; Asmussen, Hannelore; Horwitz, Alan F.

In: Journal of Cell Biology, Vol. 161, No. 1, 14.04.2003, p. 131-142.

Research output: Contribution to journalArticle

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