BIOCHEMICAL AND IMMUNOCYTOCHEMICAL CHARACTERIZATION OF GRIP, A PUTATIVE AMPA RECEPTOR ANCHORING PROTEIN, IN RAT-BRAIN

The mechanisms by which glutamate receptors are concentrated in brain excitatory synapses are believed to involve interactions between recep tor subunits and postsynaptic anchoring or scaffolding proteins. Recen tly GRIP, a protein containing seven PDZ domains, was identified as an AMPA receptor binding protein and implicated in the synaptic targetin g of AMPA receptors. Here we show that GRIP mRNA is also expressed in some tissues outside of the brain, including testis and kidney. Specif ic antibodies were raised to study GRIP protein. On Western blots, GRI P protein appears as a heterogeneous band(similar to 130 kilodaltons) which is expressed in widespread brain regions and throughout postnata l development. Biochemical studies reveal that GRIP is largely membran e associated and enriched in the postsynaptic density (PSD), though no t as highly concentrated in the PSD as is PSD-95. By immunohistochemis try, GRIP is distributed in a somatodendritic pattern in neurons of ad ult rat brain, with especially prominent expression in a subset of int erneurons. (C) 1998 Elsevier Science Ltd. All rights reserved.