Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex

Compartmentalization of glutamate receptors with the signaling enzymes that regulate their activity supports synaptic transmission. Two classes of bin ding proteins organize these complexes: the MAGUK proteins that cluster glu tamate receptors and AKAPs that anchor kinases and phosphatases. In this re port, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAG UK proteins, PSD-95 and SAP97, and AKAP79/150. The SH3 and GK regions of th e MAGUKs mediate binding to the AKAP. Cell-based studies indicate that phos phorylation of AMPA receptors is enhanced by a SAP97-AKAP79 complex that di rects PKA to GluR1 via a PDZ domain interaction. As AMPA receptor phosphory lation is implicated in regulating synaptic plasticity, these data suggest that a MAGUK-AKAP complex may be centrally involved.