Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact withsynaptic proteins of the SAPAP/GKAP family

We have recently isolated a novel proline-rich synapse-associated protein-1 (ProSAP1) that is highly enriched in postsynaptic density (PSD). A closely related multidomain protein, ProSAP2, shares a highly conserved PDZ (PSD-9 5/discs-large/ZO-1) domain (80% identity), a ppI domain that mediates the i nteraction with cortactin, and a C-terminal SAM (sterile alpha-motif) domai n. In addition, ProSAP2 codes for five ankyrin repeats and a SH3 (Src homol ogy 3) domain. Transcripts for both proteins are coexpressed in many region s of rat brain, but show a distinct expression pattern in the cerebellum. U sing the PDZ domains of ProSAP1 and 2 as bait in the yeast two-hybrid syste m, we isolated several clones of the SAPAP/GKAP (SAP90/PSD-95-associated pr otein/guanylate kinase-associated protein) family. The association of the p roteins was verified by coimmunoprecipitation and cotransfection in HEK cel ls. Therefore, proteins of the ProSAP family represent a novel Link between SAP90/PSD-95 bound membrane receptors and the cytoskeleton at glutamatergi c synapses of the central nervous system. (C) 1999 Academic Press.