Document Detail


GluN3A expression restricts spine maturation via inhibition of GIT1/Rac1 signaling.
MedLine Citation:
PMID:  24297929     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
NMDA-type glutamate receptors (NMDARs) guide the activity-dependent remodeling of excitatory synapses and associated dendritic spines during critical periods of postnatal brain development. Whereas mature NMDARs composed of GluN1 and GluN2 subunits mediate synapse plasticity and promote spine growth and stabilization, juvenile NMDARs containing GluN3A subunits are thought to inhibit these processes via yet unknown mechanisms. Here, we report that GluN3A binds G protein-coupled receptor kinase-interacting protein (GIT1), a postsynaptic scaffold that assembles actin regulatory complexes, including the Rac1 guanine nucleotide exchange factor βPIX, to promote Rac1 activation in spines. Binding to GluN3A limits the synaptic localization of GIT1 and its ability to complex βPIX, leading to decreased Rac1 activation and reduced spine density and size in primary cultured neurons. Conversely, knocking out GluN3A favors the formation of GIT1/βPIX complexes and increases the activation of Rac1 and its main effector p21-activated kinase. We further show that binding of GluN3A to GIT1 is regulated by synaptic activity, a response that might restrict the negative regulatory effects of GluN3A on actin signaling to inactive synapses. Our results identify inhibition of Rac1/p21-activated kinase actin signaling pathways as an activity-dependent mechanism mediating the inhibitory effects of GluN3A on spine morphogenesis.
Authors:
Maria Fiuza; Immaculada González-González; Isabel Pérez-Otaño
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-12-02
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  110     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-18     Completed Date:  2014-02-24     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20807-12     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics,  metabolism
Animals
Cell Cycle Proteins / genetics,  metabolism*
Cells, Cultured
Enzyme Activation / physiology
Gene Expression Regulation, Developmental / physiology*
Morphogenesis / physiology
Phosphoproteins / genetics,  metabolism*
Protein Binding / physiology
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / genetics,  metabolism*
Rho Guanine Nucleotide Exchange Factors / genetics,  metabolism
Signal Transduction / physiology*
Spine / cytology,  embryology*
Synapses / genetics,  metabolism*
rac1 GTP-Binding Protein / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Actins; 0/Cell Cycle Proteins; 0/Git1 protein, rat; 0/Phosphoproteins; 0/Receptors, N-Methyl-D-Aspartate; 0/Rho Guanine Nucleotide Exchange Factors; EC 3.6.1.-/Rac1 protein, rat; EC 3.6.5.2/rac1 GTP-Binding Protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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