RGD Reference Report - Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by Metabotropic Glutamate Receptors. - Rat Genome Database

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Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by Metabotropic Glutamate Receptors.

Authors: Kalinowska, Magdalena  Chávez, Andrés E  Lutzu, Stefano  Castillo, Pablo E  Bukauskas, Feliksas F  Francesconi, Anna 
Citation: Kalinowska M, etal., J Biol Chem. 2015 Jun 26;290(26):15909-20. doi: 10.1074/jbc.M115.640136. Epub 2015 May 5.
RGD ID: 405650279
Pubmed: PMID:25944910   (View Abstract at PubMed)
PMCID: PMC4481196   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M115.640136   (Journal Full-text)

Dendritic spines are dynamic, actin-rich protrusions in neurons that undergo remodeling during neuronal development and activity-dependent plasticity within the central nervous system. Although group 1 metabotropic glutamate receptors (mGluRs) are critical for spine remodeling under physiopathological conditions, the molecular components linking receptor activity to structural plasticity remain unknown. Here we identify a Ca(2+)-sensitive actin-binding protein, α-actinin-4, as a novel group 1 mGluR-interacting partner that orchestrates spine dynamics and morphogenesis in primary neurons. Functional silencing of α-actinin-4 abolished spine elongation and turnover stimulated by group 1 mGluRs despite intact surface receptor expression and downstream ERK1/2 signaling. This function of α-actinin-4 in spine dynamics was underscored by gain-of-function phenotypes in untreated neurons. Here α-actinin-4 induced spine head enlargement, a morphological change requiring the C-terminal domain of α-actinin-4 that binds to CaMKII, an interaction we showed to be regulated by group 1 mGluR activation. Our data provide mechanistic insights into spine remodeling by metabotropic signaling and identify α-actinin-4 as a critical effector of structural plasticity within neurons.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Actn4Ratglutamatergic synapse is_active_inIDA PMID:25944910SynGO 
Actn4Ratglutamatergic synapse is_active_inIMP PMID:25944910SynGO 
Actn4Ratpostsynaptic actin cytoskeleton is_active_inIDA PMID:25944910SynGO 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Actn4Ratstructural constituent of postsynaptic actin cytoskeleton enablesIDA PMID:25944910SynGO 
Actn4Ratstructural constituent of postsynaptic actin cytoskeleton enablesIMP PMID:25944910SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Actn4  (actinin alpha 4)


Additional Information