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Neuron. 2001 Aug 2;31(2):289-303.

Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP.

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  • 1Department of Neurobiology, Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Abstract

The PSD-95/SAP90 family of scaffold proteins organizes the postsynaptic density (PSD) and regulates NMDA receptor signaling at excitatory synapses. We report that SPAR, a Rap-specific GTPase-activating protein (RapGAP), interacts with the guanylate kinase-like domain of PSD-95 and forms a complex with PSD-95 and NMDA receptors in brain. In heterologous cells, SPAR reorganizes the actin cytoskeleton and recruits PSD-95 to F-actin. In hippocampal neurons, SPAR localizes to dendritic spines and causes enlargement of spine heads, many of which adopt an irregular appearance with putative multiple synapses. Dominant negative SPAR constructs cause narrowing and elongation of spines. The effects of SPAR on spine morphology depend on the RapGAP and actin-interacting domains, implicating Rap signaling in the regulation of postsynaptic structure.

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PMID:
11502259
[PubMed - indexed for MEDLINE]
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