title: Agonist-induced internalization of mGluR1alpha is mediated by caveolin.
abstract: Agonist-induced internalization of metabotropic glutamate receptors (mGluRs) plays an important role in neuronal signaling. Although internalization of mGluRs has been reported to be mediated by clathrin-dependent pathway, studies describing clathrin-independent pathways are emerging. Here, we report that agonist-induced internalization of mGluR1alpha is mediated by caveolin. We show that two caveolin-binding motifs of mGluR1alpha interact with caveolin1/2. Using cell surface-immunoprecipitation and total internal reflection fluorescence imaging, we found that agonist-induced internalization of mGluR1alpha is regulated by caveolin-binding motifs of the receptor in heterologous cells. Moreover, in the cerebellum, group I mGluR agonist dihydroxyphenylglycol increased the interaction of phosphorylated caveolin with mGluR1alpha. This interaction was blocked by methyl-beta-cyclodextrin, known to disrupt caveolin/caveolae-dependent signaling by cholesterol depletion. Methyl-beta-cyclodextrin also blocked the agonist-induced internalization of mGluR1alpha. Thus, these findings represent the evidence for agonist-induced internalization of mGluR1alpha via caveolin and suggest that caveolin might play a role in synaptic metaplasticity by regulating internalization of mGluR1alpha in the cerebellum.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yun Hwa
authors.initials: YH
authors.lastname: Hong
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Hong Gu
authors.initials: HG
authors.lastname: Chae
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Jang
authors.forename: Ju Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Jun
authors.initials: J
authors.lastname: Kim
authors.forename: Sang Jeong
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002277:Carcinoma; D022461:Caveolins / Q000378:metabolism*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D022461:Caveolins; D018690:Excitatory Amino Acid Agonists; D008164:Luminescent Proteins; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D016318:Quisqualic Acid; D002118:Calcium