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J Biol Chem. 2015 Jun 26;290(26):15909-20. doi: 10.1074/jbc.M115.640136. Epub 2015 May 5.

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

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From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
From the Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461


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.


Ca2+/calmodulin-dependent protein kinase II (CaMKII); actin-binding proteins; actinin; dendritic protrusion dynamics; dendritic spine; metabotropic glutamate receptor (mGluR); neuron; synaptic plasticity

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