Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 1999 Jul;23(3):583-92
Date
08/05/1999Pubmed ID
10433269DOI
10.1016/s0896-6273(00)80810-7Scopus ID
2-s2.0-0033166537 (requires institutional sign-in at Scopus site) 958 CitationsAbstract
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.
Author List
Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, Doan A, Aakalu VK, Lanahan AA, Sheng M, Worley PFAuthor
Vinay Kumar Aakalu MPH, MD Chair, Professor in the Ophthalmology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Binding Sites
COS Cells
Calcium
Calcium Channels
Carrier Proteins
Disks Large Homolog 4 Protein
Homer Scaffolding 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
SAP90-PSD95 Associated Proteins
Synapses
Transfection
