First Author | Kato AS | Year | 2012 |
Journal | J Neurosci | Volume | 32 |
Issue | 44 | Pages | 15296-308 |
PubMed ID | 23115168 | Mgi Jnum | J:192293 |
Mgi Id | MGI:5464263 | Doi | 10.1523/JNEUROSCI.0705-12.2012 |
Citation | Kato AS, et al. (2012) Glutamate receptor delta2 associates with metabotropic glutamate receptor 1 (mGluR1), protein kinase Cgamma, and canonical transient receptor potential 3 and regulates mGluR1-mediated synaptic transmission in cerebellar Purkinje neurons. J Neurosci 32(44):15296-308 |
abstractText | Cerebellar motor coordination and cerebellar Purkinje cell synaptic function require metabotropic glutamate receptor 1 (mGluR1, Grm1). We used an unbiased proteomic approach to identify protein partners for mGluR1 in cerebellum and discovered glutamate receptor delta2 (GluRdelta2, Grid2, GluDelta2) and protein kinase Cgamma (PKCgamma) as major interactors. We also found canonical transient receptor potential 3 (TRPC3), which is also needed for mGluR1-dependent slow EPSCs and motor coordination and associates with mGluR1, GluRdelta2, and PKCgamma. Mutation of GluRdelta2 changes subcellular fractionation of mGluR1 and TRPC3 to increase their surface expression. Fitting with this, mGluR1-evoked inward currents are increased in GluRdelta2 mutant mice. Moreover, loss of GluRdelta2 disrupts the time course of mGluR1-dependent synaptic transmission at parallel fiber-Purkinje cells synapses. Thus, GluRdelta2 is part of the mGluR1 signaling complex needed for cerebellar synaptic function and motor coordination, explaining the shared cerebellar motor phenotype that manifests in mutants of the mGluR1 and GluRdelta2 signaling pathways. |