Coupling of mGluR/Homer and PSD-95 complexes by the shank family of postsynaptic density proteins

Shank is a recently described family of postsynaptic proteins that function as part of the NMDA receptor-associated PSD-95 complex (Naisbitt et al., 1 999 [this issue of Neuron]). Here, we report that Shank proteins also bind to Homer. Homer proteins form multivalent complexes that bind proline-rich motifs in group 1 metabotropic glutamate receptors and inositol trisphospha te receptors, thereby coupling these receptors in a signaling complex. A si ngle Homer-binding site is identified in Shank, and Shank and Homer coimmun oprecipitate from brain and colocalize at postsynaptic densities. Moreover, Shank clusters mGluR5 in heterologous cells in the presence of Homer and m ediates the coclustering of Homer with PSD-95/GKAP. Thus, Shank may cross-l ink Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors.