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

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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 - 1 Jan 1999

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N-Methyl-D-Aspartate Receptors
Post-Synaptic Density
Inositol
Proline
Proteins
Binding Sites
Neurons
Brain
postsynaptic density proteins
metabotropic glutamate receptor type 1
Homer Scaffolding Proteins

Cite this

Tu, J. C., Xiao, B., Naisbitt, S., Yuan, J. P., Petralia, R. S., Brakeman, P., ... 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
Tu, Jian Cheng ; Xiao, Bo ; Naisbitt, Scott ; Yuan, Joseph P. ; Petralia, Ronald S. ; Brakeman, Paul ; Doan, Andrew ; Aakalu, Vinay K. ; Lanahan, Anthony A. ; Sheng, Morgan ; Worley, Paul F. / Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. In: Neuron. 1999 ; Vol. 23, No. 3. pp. 583-592.
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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.",
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Tu, JC, Xiao, B, Naisbitt, S, Yuan, JP, Petralia, RS, Brakeman, P, Doan, A, Aakalu, VK, Lanahan, AA, Sheng, M & Worley, PF 1999, 'Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins', Neuron, vol. 23, no. 3, pp. 583-592. https://doi.org/10.1016/S0896-6273(00)80810-7

Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. / Tu, Jian Cheng; Xiao, Bo; Naisbitt, Scott; Yuan, Joseph P.; Petralia, Ronald S.; Brakeman, Paul; Doan, Andrew; Aakalu, Vinay K.; Lanahan, Anthony A.; Sheng, Morgan; Worley, Paul F.

In: Neuron, Vol. 23, No. 3, 01.01.1999, p. 583-592.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Tu, Jian Cheng

AU - Xiao, Bo

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AU - Doan, Andrew

AU - Aakalu, Vinay K.

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AU - Worley, Paul F.

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