HETEROMULTIMERIZATION AND NMDA RECEPTOR-CLUSTERING ACTIVITY OF CHAPSYN-110, A MEMBER OF THE PSD-95 FAMILY OF PROTEINS

Chapsyn-110, a novel membrane-associated putative guanylate kinase (MA GUK) that binds directly to N-methyl-D-aspartate (NMDA) receptor and S haker K+ channel subunits, is 70%-80% identical to, and shares an iden tical domain organization with, PSD-95/SAP90 and SAP97. In rat brain, chapsyn-110 protein shows a somatodendritic expression pattern that ov erlaps partly with PSD-95 but that contrasts with the axonal distribut ion of SAP97. Chapsyn-110 associates tightly with the postsynaptic den sity in brain, and mediates the clustering of both NMDA receptors and K+ channels in heterologous cells. Indeed, chapsyn-110 and PSD-95 can heteromultimerize with each other and are recruited into the same NMDA receptor and K, channel clusters. Thus, chapsyn-110 and PSD-95 may in teract at postsynaptic sites to form a multimeric scaffold for the clu stering of receptors, ion channels, and associated signalling proteins .