Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin

NMDA receptors are linked to intracellular cytoskeletal and signaling molec ules via the PSD-95 protein complex. We report a novel family of postsynapt ic density (PSD) proteins, termed Shank, that binds via its PDZ domain to t he C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank /GKAP/PSD-95 assembles in heterologous cells and can be coimmunoprecipitate d from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cort actin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD -95 complexes and coupling them to regulators of the actin cytoskeleton.