title: Synaptic ERK2 Phosphorylates and Regulates Metabotropic Glutamate Receptor 1 In Vitro and in Neurons.
abstract: A synaptic pool of extracellular signal-regulated kinases (ERK) controls synaptic transmission, although little is known about its underlying signaling mechanisms. Here, we found that synaptic ERK2 directly binds to postsynaptic metabotropic glutamate receptor 1a (mGluR1a). This binding is direct and the ERK-binding site is located in the intracellular C-terminus (CT) of mGluR1a. Parallel with this binding, ERK2 phosphorylates mGluR1a at a cluster of serine residues in the distal part of mGluR1a-CT. In rat cerebellar neurons, ERK2 interacts with mGluR1a at synaptic sites, and active ERK constitutively phosphorylates mGluR1a under normal conditions. This basal phosphorylation is critical for maintaining adequate surface expression of mGluR1a. ERK is also essential for controlling mGluR1a signaling in triggering distinct postreceptor signaling transduction pathways. In summary, we have demonstrated that mGluR1a is a sufficient substrate of ERK2. ERK that interacts with and phosphorylates mGluR1a is involved in the regulation of the trafficking and signaling of mGluR1.
authors: Department of Biological Sciences, Pusan National University, Busan, 46241, South Korea.
authors: Ju Hwan
authors: JH
authors: Yang
authors: Department of Anesthesiology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
authors: Li-Min
authors: LM
authors: Mao
authors: Department of Biological Sciences, Pusan National University, Busan, 46241, South Korea. eschoe@pusan.ac.kr.
authors: Eun Sang
authors: ES
authors: Choe
authors: Department of Anesthesiology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA. wangjq@umkc.edu.|Beijing Institute of Brain Disorders, Capital Medical University, Beijing, 100069, China. wangjq@umkc.edu.
authors: John Q
authors: JQ
authors: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D002070:Butadienes; D009570:Nitriles; D018094:Receptors, Metabotropic Glutamate; C113580:U 0126; C104077:metabotropic glutamate receptor type 1; D010768:Phosphoserine; D015544:Inositol 1,4,5-Trisphosphate; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1
keywords: Cerebellum; G protein-coupled receptor; IP3; MAPK; Phosphorylation; Src; mGluR