PMID- 10433269 OWN - NLM STAT- MEDLINE DCOM- 19990813 LR - 20190822 IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 23 IP - 3 DP - 1999 Jul TI - Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. PG - 583-92 AB - 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. FAU - Tu, J C AU - Tu JC AD - Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. FAU - Xiao, B AU - Xiao B FAU - Naisbitt, S AU - Naisbitt S FAU - Yuan, J P AU - Yuan JP FAU - Petralia, R S AU - Petralia RS FAU - Brakeman, P AU - Brakeman P FAU - Doan, A AU - Doan A FAU - Aakalu, V K AU - Aakalu VK FAU - Lanahan, A A AU - Lanahan AA FAU - Sheng, M AU - Sheng M FAU - Worley, P F AU - Worley PF LA - eng GR - DA10309/DA/NIDA NIH HHS/United States GR - DA11742/DA/NIDA NIH HHS/United States GR - KO2 MH01152/MH/NIMH NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Neuron JT - Neuron JID - 8809320 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Calcium Channels) RN - 0 (Carrier Proteins) RN - 0 (DLGAP1 protein, human) RN - 0 (Disks Large Homolog 4 Protein) RN - 0 (Dlg4 protein, rat) RN - 0 (Homer Scaffolding Proteins) RN - 0 (ITPR1 protein, human) RN - 0 (Inositol 1,4,5-Trisphosphate Receptors) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuropeptides) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Metabotropic Glutamate) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (SAP90-PSD95 Associated Proteins) RN - 0 (SHANK3 protein, human) RN - 0 (Shank1 protein, rat) RN - 0 (Shank3 protein, rat) RN - 0 (metabotropic glutamate receptor type 1) RN - 0 (postsynaptic density proteins) RN - 9DLQ4CIU6V (Proline) RN - SY7Q814VUP (Calcium) SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Animals MH - Binding Sites/physiology MH - COS Cells MH - Calcium/metabolism MH - Calcium Channels/metabolism MH - Carrier Proteins/chemistry/genetics/*metabolism MH - Disks Large Homolog 4 Protein MH - Homer Scaffolding Proteins MH - Humans MH - Inositol 1,4,5-Trisphosphate Receptors MH - Intracellular Signaling Peptides and Proteins MH - Kidney/cytology MH - Membrane Proteins MH - Microscopy, Immunoelectron MH - Mutagenesis, Site-Directed/physiology MH - Nerve Tissue Proteins/*metabolism MH - Neurons/*chemistry/metabolism MH - Neuropeptides/chemistry/*metabolism MH - Proline/metabolism MH - Protein Structure, Tertiary MH - Rabbits MH - Rats MH - Receptors, Cytoplasmic and Nuclear/metabolism MH - Receptors, Metabotropic Glutamate/*metabolism MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - SAP90-PSD95 Associated Proteins MH - Synapses/chemistry/metabolism/ultrastructure MH - Transfection EDAT- 1999/08/05 00:00 MHDA- 1999/08/05 00:01 CRDT- 1999/08/05 00:00 PHST- 1999/08/05 00:00 [pubmed] PHST- 1999/08/05 00:01 [medline] PHST- 1999/08/05 00:00 [entrez] AID - S0896-6273(00)80810-7 [pii] AID - 10.1016/s0896-6273(00)80810-7 [doi] PST - ppublish SO - Neuron. 1999 Jul;23(3):583-92. doi: 10.1016/s0896-6273(00)80810-7.