Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha-actinin2.
Rap small GTPases regulate excitatory synaptic strength and morphological plasticity of dendritic spines. Changes in spine structure are mediated by the F-actin cytoskeleton, but the link between Rap activity and actin dynamics is unclear. Here, we report a novel interaction between SPAR, a postsynaptic inhibitor of Rap, and alpha-actinin, a family of actin-cross-linking proteins. SPAR and alpha-actinin engage in bidirectional structural plasticity of dendritic spines: SPAR promotes spine head enlargement, whereas increased alpha-actinin2 expression favors dendritic spine elongation and thinning. Surprisingly, SPAR and alpha-actinin2 can function in an additive rather than antagonistic fashion at the same dendritic spine, generating combination spine/filopodia hybrids. These data identify a molecular pathway bridging the actin cytoskeleton and Rap at synapses, and suggest that formation of spines and filopodia are not necessarily opposing forms of structural plasticity.
Hoe
Hyang-Sook
HS
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA.
Lee
Ji-Yun
JY
Pak
Daniel T S
DT
D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D020798:Two-Hybrid System Techniques
C116934:E6-target protein 1; D020690:GTPase-Activating Proteins; D000185:Actinin