Actinin-4 governs dendritic spine dynamics and promotes their remodeling by metabotropic glutamate receptors

Magdalena Kalinowska, Andrés E. Chávez, Stefano Lutzu, Pablo E. Castillo, Feliksas F. Bukauskas, Anna Francesconi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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<sup>2+</sup>-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.

Original languageEnglish (US)
Pages (from-to)15909-15920
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number26
DOIs
StatePublished - Jun 26 2015

Fingerprint

Actinin
Dendritic Spines
Metabotropic Glutamate Receptors
Spine
Neurons
Plasticity
Microfilament Proteins
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Neuronal Plasticity
Neurology
Morphogenesis
Actins
Elongation
Central Nervous System
Chemical activation
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Actinin-4 governs dendritic spine dynamics and promotes their remodeling by metabotropic glutamate receptors. / Kalinowska, Magdalena; Chávez, Andrés E.; Lutzu, Stefano; Castillo, Pablo E.; Bukauskas, Feliksas F.; Francesconi, Anna.

In: Journal of Biological Chemistry, Vol. 290, No. 26, 26.06.2015, p. 15909-15920.

Research output: Contribution to journalArticle

Kalinowska, Magdalena ; Chávez, Andrés E. ; Lutzu, Stefano ; Castillo, Pablo E. ; Bukauskas, Feliksas F. ; Francesconi, Anna. / Actinin-4 governs dendritic spine dynamics and promotes their remodeling by metabotropic glutamate receptors. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 26. pp. 15909-15920.
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