Agonist-induced internalization of mGluR1alpha is mediated by caveolin.
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.
Hong
Yun Hwa
YH
Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
Kim
Ji Young
JY
Lee
Jeong Ho
JH
Chae
Hong Gu
HG
Jang
Sung Soo
SS
Jeon
Ju Hong
JH
Kim
Chul Hoon
CH
Kim
Jun
J
Kim
Sang Jeong
SJ
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
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