Tyrosine phosphorylation of the metabotropic glutamate receptor mGluR5 in striatal neurons.
Protein phosphorylation, controlled by the coordinated actions of phosphatases and kinases, is an important regulatory mechanism in synaptic transmission and other neurophysiological processes. Ionotropic glutamate receptors are known targets of phosphorylation on serine, threonine and tyrosine residues, with functional consequences for cell excitability, plasticity and toxicity. While phosphorylation of metabotropic glutamate receptors (mGluRs) also impacts critical cellular processes, there has been no evidence for direct tyrosine phosphorylation of mGluRs. In the present study, anti-phosphotyrosine and specific mGluR antibodies were used to detect tyrosine-phosphorylated mGluRs in rat brain. In particular, we found that mGluR5 is an abundant phosphotyrosine protein in vivo as well as in primary striatal neurons and tissue slices in vitro. The protein phosphatase inhibitor pervanadate robustly increased the amount of tyrosine-phosphorylated mGluR5, suggesting the receptor is subject to an endogenous, active cycle of phosphorylation and dephosphorylation. Furthermore, NMDA treatment also increased the amount of tyrosine-phosphorylated mGluR5, suggesting these endogenous phosphorylation regulatory mechanisms can be used to mediate crosstalk between synaptic glutamate receptors. While mGluR5-stimulated phosphoinositide hydrolysis appears to be unaltered by pervanadate treatment, tyrosine phosphorylation of mGluR5 may be important in trafficking, anchoring, or signaling of the receptor through G protein-independent pathways.
Orlando
L R
LR
Program in Neuroscience, Harvard Medical School, and Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. orlando@helix.mgh.harvard.edu
Dunah
A W
AW
Standaert
D G
DG
Young
A B
AB
D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D004622:Embryo, Mammalian; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014443:Tyrosine