title: Regulation of mGluR7 trafficking by SUMOylation in neurons.
abstract: SUMOylation is a post-translational modification by which Small Ubiquitin-like MOdifier (SUMO) proteins are covalently linked to the lysine residues of target proteins via an enzymatic cascade. SUMOylation at the synapse plays an important regulatory role in a wide variety of neuronal function such as synapse formation and receptor endocytosis. The metabotropic glutamate receptor type 7 (mGluR7), a presynaptic G protein-coupled receptor, modulates excitatory neurotransmission and synaptic plasticity by inhibiting neurotransmitter release. The SUMO conjugation of mGluR7 has been demonstrated from several in vitro studies, however, it has not been successful in identifying SUMOylation of full-length mGluR7 in vivo. In the present study, we find that mGluR7 at Lys889 is a target of SUMO conjugation, which is impeded by SUMO-specific isopeptidase SENP1 in HEK 293T cells. In addition, we identify SUMOylated mGluR7 both in brain and primary cortical neurons, that is reduced by the treatment of L-AP4, mGluR7 agonist. We find that deSUMOylated mutation in mGluR7 or overexpression of SENP-1 markedly increases mGluR7 internalization in hippocampal neurons, indicating that endocytosis of mGluR7 is enhanced by the reduced SUMO conjugation of mGluR7. Furthermore, Ser862 phosphorylation facilitates SUMO conjugation of mGluR7. Together, these results reveal that SUMOylation of mGluR7 at Lys889 is required for stable surface expression of mGluR7 in neurons.
authors.affiliation: Department of Pharmacology and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, 443-721, South Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Pharmacology and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, 443-721, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, 110-799, South Korea.
authors.forename: Seung Pyo
authors.initials: SP
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, 110-799, South Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, 110-799, South Korea.
authors.forename: Seulki
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pharmacology and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, 443-721, South Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Pharmacology and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, 443-721, South Korea; Department of Biomedical Sciences and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, 110-799, South Korea. Electronic address: suhyho@snu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Suh
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D058207:Sumoylation / Q000187:drug effects / Q000502:physiology*
chemical_list: C114785:2-amino-4-phosphono-propinate; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7
keywords: L-AP4 (PubChem CID: 179394); PMA (PubChem CID: 27924); Phosphorylation; SUMOylation; Trafficking; mGluR7