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

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(2+)-sensitive actin-binding protein, ?-actinin-4, as a novel group 1 mGluR-interacting partner that orchestrates spine dynamics and morphogenesis in primary neurons. Functional silencing of ?-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 ?-actinin-4 in spine dynamics was underscored by gain-of-function phenotypes in untreated neurons. Here ?-actinin-4 induced spine head enlargement, a morphological change requiring the C-terminal domain of ?-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 ?-actinin-4 as a critical effector of structural plasticity within neurons.

SUBMITTER: Kalinowska M 

PROVIDER: S-EPMC4481196 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature