Basic Fibroblast Growth Factor Modulates the Expression of PDZ Domain-containing Proteins in Cultured Cortical Neurons.

Abstract

Different cytokines and growth factors, together with their receptors, are expressed in brain tissue. One such molecule is the basic fibroblast growth factor (bFGF) that has recently been shown to promote survival following insults to neurons in vivo or in vitro. In this study, we found that repeated treatment of neocortical cultures with bFGF modulated the expression of various PDZ domain-containing proteins (SAP97, GRIP1, Pick1, and PSD-93) and that the patterns of their immunostaining matched the bFGF effects on their total protein expression. For instance, bFGF decreased the expression of SAP97, GRIP1, and Pick1 (PDZ proteins that interact with the AMPA-type glutamate receptor subunits GluR1 and GluR2/3). PSD-93, which associates with the NMDA-type glutamate receptor, was increased by bFGF. Moreover, the interactions of GluR1 with SAP97 and GluR2 with GRIP1 were down-regulated by the repeated bFGF stimulation, as revealed by co-immunoprecipitation. Together, these results describe a novel function of bFGF in the regulation of expression of PDZ proteins.