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

13 Scopus citations

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 Ca2+-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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Actinin-4 governs dendritic spine dynamics and promotes their remodeling by metabotropic glutamate receptors'. Together they form a unique fingerprint.

  • Cite this