Agonist-induced internalization of mGluR1α is mediated by caveolin |
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Authors: | Yun Hwa Hong Ji Young Kim Jeong Ho Lee† Hong Gu Chae Sung Soo Jang Ju Hong Jeon Chul Hoon Kim† Jun Kim Sang Jeong Kim‡ |
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Institution: | Department of Physiology, Seoul National University College of Medicine, Seoul, Korea; Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; Department of Brain and Cognitive Neuroscience, Seoul National University, Seoul, Korea |
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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 mGluR1α is mediated by caveolin. We show that two caveolin-binding motifs of mGluR1α interact with caveolin1/2. Using cell surface-immunoprecipitation and total internal reflection fluorescence imaging, we found that agonist-induced internalization of mGluR1α 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 mGluR1α. This interaction was blocked by methyl-β-cyclodextrin, known to disrupt caveolin/caveolae-dependent signaling by cholesterol depletion. Methyl-β-cyclodextrin also blocked the agonist-induced internalization of mGluR1α. Thus, these findings represent the evidence for agonist-induced internalization of mGluR1α via caveolin and suggest that caveolin might play a role in synaptic metaplasticity by regulating internalization of mGluR1α in the cerebellum. |
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Keywords: | agonist-induced internalization caveolin cerebellum mGluR1α |
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