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., 1999 [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 trisphosphate receptors, thereby coupling these receptors in a signaling complex. A single Homer-binding site is identified in Shank, and Shank and Homer coimmunoprecipitate from brain and colocalize at postsynaptic densities. Moreover, Shank clusters mGluR5 in heterologous cells in the presence of Homer and mediates the coclustering of Homer with PSD-95/GKAP. Thus, Shank may cross-link Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Binding Sites, COS Cells, Calcium, Calcium Channels, Carrier Proteins, Humans, Inositol 1,4,5-Trisphosphate Receptors, Intracellular Signaling Peptides and Proteins, Kidney, Membrane Proteins, Microscopy, Immunoelectron, Mutagenesis, Site-Directed, Nerve Tissue Proteins, Neurons, Neuropeptides, Proline, Protein Structure, Tertiary, Rabbits, Rats, Receptors, Cytoplasmic and Nuclear, Receptors, Metabotropic Glutamate, Receptors, N-Methyl-D-Aspartate, Synapses, Transfection
Neuron
Date: Jul. 01, 1999
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