Journal
JOURNAL OF NEUROCHEMISTRY
Volume 111, Issue 1, Pages 61-71Publisher
WILEY
DOI: 10.1111/j.1471-4159.2009.06289.x
Keywords
agonist-induced internalization; caveolin; cerebellum; mGluR1 alpha
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Funding
- Ministry of Education, Science and Technology [2009-0080939, R32-10142]
- National Research Foundation of Korea [2009-0080939] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 mGluR1 alpha is mediated by caveolin. We show that two caveolin-binding motifs of mGluR1 alpha interact with caveolin1/2. Using cell surface-immunoprecipitation and total internal reflection fluorescence imaging, we found that agonist-induced internalization of mGluR1 alpha 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 mGluR1 alpha. 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 mGluR1 alpha. Thus, these findings represent the evidence for agonist-induced internalization of mGluR1 alpha via caveolin and suggest that caveolin might play a role in synaptic metaplasticity by regulating internalization of mGluR1 alpha in the cerebellum.
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