title: GRASP-1: a neuronal RasGEF associated with the AMPA receptor/GRIP complex.
abstract: The PDZ domain-containing proteins, such as PSD-95 and GRIP, have been suggested to be involved in the targeting of glutamate receptors, a process that plays a critical role in the efficiency of synaptic transmission and plasticity. To address the molecular mechanisms underlying AMPA receptor synaptic localization, we have identified several GRIP-associated proteins (GRASPs) that bind to distinct PDZ domains within GRIP. GRASP-1 is a neuronal rasGEF associated with GRIP and AMPA receptors in vivo. Overexpression of GRASP-1 in cultured neurons specifically reduced the synaptic targeting of AMPA receptors. In addition, the subcellular distribution of both AMPA receptors and GRASP-1 was rapidly regulated by the activation of NMDA receptors. These results suggest that GRASP-1 may regulate neuronal ras signaling and contribute to the regulation of AMPA receptor distribution by NMDA receptor activity.
authors.affiliation: Howard Hughes Medical Institute, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ye
authors.forename: D
authors.initials: D
authors.lastname: Liao
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.forename: R L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003001:Cloning, Molecular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013379:Substrate Specificity; D013569:Synapses / Q000378:metabolism; D014018:Tissue Distribution; D020663:ras Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C485827:GRIPAP1 protein, human; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D020663:ras Guanine Nucleotide Exchange Factors; C410230:tamalin protein, human; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases