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

Jian Cheng Tu, Bo Xiao, Scott Naisbitt, Joseph P. Yuan, Ronald S. Petralia, Paul Brakeman, Andrew Doan, Vinay K. Aakalu, Anthony A. Lanahan, Morgan Sheng, Paul F. Worley

Research output: Contribution to journalArticle

815 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)583-592
Number of pages10
JournalNeuron
Volume23
Issue number3
DOIs
StatePublished - Jul 1999

Fingerprint Dive into the research topics of 'Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins'. Together they form a unique fingerprint.

  • Cite this

    Tu, J. C., Xiao, B., Naisbitt, S., Yuan, J. P., Petralia, R. S., Brakeman, P., Doan, A., Aakalu, V. K., Lanahan, A. A., Sheng, M., & Worley, P. F. (1999). Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron, 23(3), 583-592. https://doi.org/10.1016/S0896-6273(00)80810-7