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 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.
Pak
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DT
Department of Neurobiology, Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Yang
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Rudolph-Correia
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S
Kim
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Sheng
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M
D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D019556:COS Cells; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000648:ultrastructure*; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D051528:Guanylate Kinases; D006624:Hippocampus / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000648:ultrastructure; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013569:Synapses; D014162:Transfection
D000199:Actins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases