GRASP-1: a neuronal RasGEF associated with the AMPA receptor/GRIP complex

Neuron. 2000 Jun;26(3):603-17. doi: 10.1016/s0896-6273(00)81198-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Caspase 3
  • Caspases / metabolism
  • Cloning, Molecular
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Protein Isoforms / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Substrate Specificity
  • Synapses / metabolism
  • Tissue Distribution
  • ras Guanine Nucleotide Exchange Factors / genetics
  • ras Guanine Nucleotide Exchange Factors / metabolism*

Substances

  • Carrier Proteins
  • GRASP protein, human
  • GRIPAP1 protein, human
  • Grip1 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • ras Guanine Nucleotide Exchange Factors
  • CASP3 protein, human
  • Casp3 protein, rat
  • Caspase 3
  • Caspases

Associated data

  • GENBANK/AF040944
  • GENBANK/AF274057