RGD Reference Report - α-Actinin-2 mediates spine morphology and assembly of the post-synaptic density in hippocampal neurons. - Rat Genome Database

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α-Actinin-2 mediates spine morphology and assembly of the post-synaptic density in hippocampal neurons.

Authors: Hodges, Jennifer L  Vilchez, Samuel Martin  Asmussen, Hannelore  Whitmore, Leanna A  Horwitz, Alan Rick 
Citation: Hodges JL, etal., PLoS One. 2014 Jul 9;9(7):e101770. doi: 10.1371/journal.pone.0101770. eCollection 2014.
RGD ID: 405650341
Pubmed: PMID:25007055   (View Abstract at PubMed)
PMCID: PMC4090192   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0101770   (Journal Full-text)

Dendritic spines are micron-sized protrusions that constitute the primary post-synaptic sites of excitatory neurotransmission in the brain. Spines mature from a filopodia-like protrusion into a mushroom-shaped morphology with a post-synaptic density (PSD) at its tip. Modulation of the actin cytoskeleton drives these morphological changes as well as the spine dynamics that underlie learning and memory. Several PSD molecules respond to glutamate receptor activation and relay signals to the underlying actin cytoskeleton to regulate the structural changes in spine and PSD morphology. α-Actinin-2 is an actin filament cross-linker, which localizes to dendritic spines, enriched within the post-synaptic density, and implicated in actin organization. We show that loss of α-actinin-2 in rat hippocampal neurons creates an increased density of immature, filopodia-like protrusions that fail to mature into a mushroom-shaped spine during development. α-Actinin-2 knockdown also prevents the recruitment and stabilization of the PSD in the spine, resulting in failure of synapse formation, and an inability to structurally respond to chemical stimulation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor. The Ca2+-insensitive EF-hand motif in α-actinin-2 is necessary for the molecule's function in regulating spine morphology and PSD assembly, since exchanging it for the similar but Ca2+-sensitive domain from α-actinin-4, another α-actinin isoform, inhibits its function. Furthermore, when the Ca2+-insensitive domain from α-actinin-2 is inserted into α-actinin-4 and expressed in neurons, it creates mature spines. These observations support a model whereby α-actinin-2, partially through its Ca2+-insensitive EF-hand motif, nucleates PSD formation via F-actin organization and modulates spine maturation to mediate synaptogenesis.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Actn2Ratglutamatergic synapse is_active_inIDA PMID:25007055SynGO 
Actn2Ratglutamatergic synapse is_active_inIMP PMID:25007055SynGO 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Actn2Ratstructural constituent of postsynaptic actin cytoskeleton enablesIDA PMID:25007055SynGO 
Actn2Ratstructural constituent of postsynaptic actin cytoskeleton enablesIMP PMID:25007055SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Actn2  (actinin alpha 2)


Additional Information