Synapse formation is regulated by the signaling adaptor GIT1
| العنوان: | Synapse formation is regulated by the signaling adaptor GIT1 |
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| المؤلفون: | Huaye Zhang, Alan F. Horwitz, Donna J. Webb, Hannelore Asmussen |
| المصدر: | The Journal of Cell Biology |
| بيانات النشر: | Rockefeller University Press, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Dendritic spine, GTPase-activating protein, Presynaptic Terminals, Synaptic Membranes, Synaptogenesis, Cell Cycle Proteins, Biology, Hippocampus, Article, 03 medical and health sciences, Actin remodeling of neurons, 0302 clinical medicine, Postsynaptic potential, Intellectual Disability, Neural Pathways, Animals, Guanine Nucleotide Exchange Factors, Cells, Cultured, 030304 developmental biology, 0303 health sciences, GTPase-Activating Proteins, Brain, Cell Differentiation, synapse formation, GIT1, PIX, Rac, spine morphology, Dendrites, Cell Biology, Phosphoproteins, Synapsins, Actins, Rats, rac GTP-Binding Proteins, Cell biology, Rac GTP-Binding Proteins, Phenotype, Mutation, Guanine nucleotide exchange factor, Signal transduction, Rho Guanine Nucleotide Exchange Factors, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | 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. |
| تدمد: | 1540-8140 0021-9525 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::94666898e74c88ae8b4f7071c2f50f38Test https://doi.org/10.1083/jcb.200211002Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....94666898e74c88ae8b4f7071c2f50f38 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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