RGD Reference Report - Inositol 1,4,5-trisphosphate 3-kinase a functions as a scaffold for synaptic Rac signaling. - Rat Genome Database

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Inositol 1,4,5-trisphosphate 3-kinase a functions as a scaffold for synaptic Rac signaling.

Authors: Kim, IH  Park, SK  Hong, ST  Jo, YS  Kim, EJ  Park, EH  Han, SB  Shin, HS  Sun, W  Kim, HT  Soderling, SH  Kim, H 
Citation: Kim IH, etal., J Neurosci. 2009 Nov 4;29(44):14039-49. doi: 10.1523/JNEUROSCI.2483-09.2009.
RGD ID: 8553536
Pubmed: PMID:19890013   (View Abstract at PubMed)
PMCID: PMC2818627   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.2483-09.2009   (Journal Full-text)

Activity-dependent alterations of synaptic contacts are crucial for synaptic plasticity. The formation of new dendritic spines and synapses is known to require actin cytoskeletal reorganization specifically during neural activation phases. Yet the site-specific and time-dependent mechanisms modulating actin dynamics in mature neurons are not well understood. In this study, we show that actin dynamics in spines is regulated by a Rac anchoring and targeting function of inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A), independent of its kinase activity. On neural activation, IP(3)K-A bound directly to activated Rac1 and recruited it to the actin cytoskeleton in the postsynaptic area. This focal targeting of activated Rac1 induced spine formation through actin dynamics downstream of Rac signaling. Consistent with the scaffolding role of IP(3)K-A, IP(3)K-A knock-out mice exhibited defects in accumulation of PAK1 by long-term potentiation-inducing stimulation. This deficiency resulted in a reduction in the reorganization of actin cytoskeletal structures in the synaptic area of dentate gyrus. Moreover, IP(3)K-A knock-out mice showed deficits of synaptic plasticity in perforant path and in hippocampal-dependent memory performances. These data support a novel model in which IP(3)K-A is critical for the spatial and temporal regulation of spine actin remodeling, synaptic plasticity, and learning and memory via an activity-dependent Rac scaffolding mechanism.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ItpkaRatdendritic spine located_inIDA PMID:19890013MGI 
ItpkaRatglutamatergic synapse is_active_inIDA PMID:19890013SynGO 
ItpkaRatglutamatergic synapse is_active_inIEP PMID:19890013SynGO 
ItpkaRatglutamatergic synapse is_active_inIMP PMID:19890013SynGO 
ItpkaRatpostsynaptic actin cytoskeleton is_active_inIDA PMID:19890013SynGO 
ItpkaRatpostsynaptic actin cytoskeleton is_active_inIMP PMID:19890013SynGO 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ItpkaRatsmall GTPase binding enablesIDA PMID:19890013MGI 

Objects Annotated

Genes (Rattus norvegicus)
Itpka  (inositol-trisphosphate 3-kinase A)


Additional Information