RGD Reference Report - GIT1 and ßPIX are essential for GABA(A) receptor synaptic stability and inhibitory neurotransmission. - Rat Genome Database

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GIT1 and ßPIX are essential for GABA(A) receptor synaptic stability and inhibitory neurotransmission.

Authors: Smith, Katharine R  Davenport, Elizabeth C  Wei, Jing  Li, Xiangning  Pathania, Manavendra  Vaccaro, Victoria  Yan, Zhen  Kittler, Josef T 
Citation: Smith KR, etal., Cell Rep. 2014 Oct 9;9(1):298-310. doi: 10.1016/j.celrep.2014.08.061. Epub 2014 Oct 2.
RGD ID: 13702191
Pubmed: PMID:25284783   (View Abstract at PubMed)
PMCID: PMC4536293   (View Article at PubMed Central)
DOI: DOI:10.1016/j.celrep.2014.08.061   (Journal Full-text)

Effective inhibitory synaptic transmission requires efficient stabilization of GABA(A) receptors (GABA(A)Rs) at synapses, which is essential for maintaining the correct excitatory-inhibitory balance in the brain. However, the signaling mechanisms that locally regulate synaptic GABA(A)R membrane dynamics remain poorly understood. Using a combination of molecular, imaging, and electrophysiological approaches, we delineate a GIT1/ßPIX/Rac1/PAK signaling pathway that modulates F-actin and is important for maintaining surface GABA(A)R levels, inhibitory synapse integrity, and synapse strength. We show that GIT1 and ßPIX are required for synaptic GABA(A)R surface stability through the activity of the GTPase Rac1 and downstream effector PAK. Manipulating this pathway using RNAi, dominant-negative and pharmacological approaches leads to a disruption of GABA(A)R clustering and decrease in the strength of synaptic inhibition. Thus, the GIT1/ßPIX/Rac1/PAK pathway plays a crucial role in regulating GABA(A)R synaptic stability and hence inhibitory synaptic transmission with important implications for inhibitory plasticity and information processing in the brain.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Arhgef7RatGABA-ergic synapse is_active_inIMP PMID:25284783SynGO 
Arhgef7RatGABA-ergic synapse is_active_inIDA PMID:25284783SynGO 
Git1RatGABA-ergic synapse is_active_inIDA PMID:25284783SynGO 
Git1RatGABA-ergic synapse is_active_inIMP PMID:25284783SynGO 
Rac1RatGABA-ergic synapse is_active_inEXP PMID:25284783SynGO 
Rac1RatGABA-ergic synapse is_active_inIDA PMID:25284783SynGO 
Rac1RatGABA-ergic synapse is_active_inIMP PMID:25284783SynGO 
Git1Ratglutamatergic synapse is_active_inIDA PMID:25284783SynGO 
Git1Ratpostsynapse is_active_inIDA PMID:25284783SynGO 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Git1Ratstructural constituent of postsynaptic specialization enablesIDA PMID:25284783SynGO 
Git1Ratstructural constituent of postsynaptic specialization enablesIMP PMID:25284783SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Arhgef7  (Rho guanine nucleotide exchange factor 7)
Git1  (GIT ArfGAP 1)
Rac1  (Rac family small GTPase 1)


Additional Information