Regulation of Dendritic Spine Morphology by SPAR, a PSD-95-Associated RapGAP

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 wi...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2001-08, Vol.31 (2), p.289-303
Main Authors: Pak, Daniel T.S., Yang, Soyoung, Rudolph-Correia, Sheila, Kim, Eunjoon, Sheng, Morgan
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Binding Sites
Brain - metabolism
Brain - ultrastructure
Cells, Cultured
COS Cells
Cytoskeleton - drug effects
Cytoskeleton - metabolism
Dendrites - drug effects
Dendrites - ultrastructure
Disks Large Homolog 4 Protein
Embryo, Mammalian
GTPase-Activating Proteins - chemistry
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - pharmacology
Guanylate Kinases
Hippocampus - ultrastructure
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Mutagenesis
Nerve Tissue Proteins - metabolism
Neurons - ultrastructure
Nucleoside-Phosphate Kinase - metabolism
postsynaptic density 95 protein
Rap protein
Rats
Receptors, N-Methyl-D-Aspartate - metabolism
Saccharomyces cerevisiae - genetics
Synapses
Transfection
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(01)00355-5