Abstract
Appropriate trafficking and targeting of glutamate receptors (GluRs) to the postsynaptic density is crucial for synaptic function. We show that mPins (mammalian homologue of Drosophila melanogaster partner of inscuteable) interacts with SAP102 and PSD-95 (two PDZ proteins present in neurons), and functions in the formation of the NMDAR–MAGUK (N-methyl-D-aspartate receptor–membrane-associated guanylate kinase) complex. mPins enhances trafficking of SAP102 and NMDARs to the plasma membrane in neurons. Expression of dominant–negative constructs and short-interfering RNA (siRNA)-mediated knockdown of mPins decreases SAP102 in dendrites and modifies surface expression of NMDARs. mPins changes the number and morphology of dendritic spines and these effects depend on its Gαi interaction domain, thus implicating G-protein signalling in the regulation of postsynaptic structure and trafficking of GluRs.
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Acknowledgements
We thank C.C. Garner for providing the SAP102 cDNA, D. Bredt for the PSD-95 and PSD-95 C3,5S GFP-tagged constructs, A. El-Husseini for the GKAP construct, D.B. Arnold for the Kv1.4 construct, A. Stephenson for the Flag-tagged NR2B construct, K.W. Roche for the Tac constructs, and J. Hell for the SAP102 antibody. We thank K. Prybylowski and L.A. Dunbar for discussion and helpful suggestions. We also thank M. Montcouquiol and S. M. Lanier for valuable comments on the manuscript. Animals were handled in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. Supported by the Intramural Research Program of the National Institute on Deafness and Other Communication Disorders (NIDCD), NIH grant GM070902 to I.M., and NIH grant F32MH65092 to J.B.
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Sans, N., Wang, P., Du, Q. et al. mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression. Nat Cell Biol 7, 1179–1190 (2005). https://doi.org/10.1038/ncb1325
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DOI: https://doi.org/10.1038/ncb1325
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