GRIP1

GRIP1, or Glutamate Receptor Interacting Protein 1, is a neuronal scaffolding protein that participates in the trafficking and localization of AMPA-type glutamate receptors. The GRIP1 gene in humans encodes multiple isoforms that contain PDZ domains, enabling interactions with the C-terminal tails of AMPA receptor subunits GluA2 (GRIA2) and GluA3 (GRIA3). Through these interactions, GRIP1 helps assemble receptor-containing complexes at the postsynaptic density.

GRIP1 functions as a postsynaptic scaffold that couples AMPA receptors to the cytoskeleton and trafficking machinery. It forms complexes with other scaffolding proteins such as PSD-95 and liprin-α, and can influence receptor delivery to and stabilization at synapses. GRIP1 operates in concert with or in opposition to other PDZ-domain proteins like PICK1; while PICK1 promotes internalization, GRIP1 promotes membrane stabilization of GluA2/3-containing receptors. The binding to GluA2/3 and the receptor's trafficking are regulated by synaptic activity and post-translational modifications.

Expression studies show GRIP1 is enriched in the brain, with notable expression in the hippocampus and cortex. Alternative splicing yields several isoforms that differ in PDZ domain composition and subcellular localization. By modulating AMPA receptor availability at the synapse, GRIP1 contributes to synaptic plasticity mechanisms including long-term potentiation and long-term depression.