Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 290, Issue 48, Pages 28613-28622Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.R115.655118
Keywords
actin; adhesion; Arp2; 3 complex; cofilin; dendritic spine; formin; Rho (Rho GTPase); synapse; synaptic plasticity; WASH
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Funding
- National Institutes of Health Grants [MH103374, NS059957]
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The small size of dendritic spines belies the elaborate role they play in excitatory synaptic transmission and ultimately complex behaviors. The cytoskeletal architecture of the spine is predominately composed of actin filaments. These filaments, which at first glance might appear simple, are also surprisingly complex. They dynamically assemble into different structures and serve as a platform for orchestrating the elaborate responses of the spine during spinogenesis and experience-dependent plasticity. Multiple mutations associated with human neurodevelopmental and psychiatric disorders involve genes that encode regulators of the synaptic cytoskeleton. A major, unresolved question is how the disruption of specific actin filament structures leads to the onset and progression of complex synaptic and behavioral phenotypes. This review will cover established and emerging mechanisms of actin cytoskeletal remodeling and how this influences specific aspects of spine biology that are implicated in disease.
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