Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 47, Pages 11335-11352Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1223-17.2017
Keywords
autism; metabotropic glutamate receptor; motor coordination; purkinje cell; trafficking; transferrin receptor
Categories
Funding
- National Natural Science Foundation of China [81625006, 31471024, 31571051]
- Natural Science Foundation of Zhejiang Province [Z15C090001, LY15C090001]
- Chinese Ministry of Education (Project 111 Program) [B13026]
- Zhejiang Province Medical and Health Research Foundation [2017200463]
- Dutch Organization for Medical Sciences and Life Sciences
- ERC-adv of the European Union
- ERC-POC of the European Union
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Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice. Weshow that conditional knock-out of TFR1 in PCs does not affect the cytoarchitecture of PCs, but reduces mGlu1 expression at synapses. This regulation by TFR1acts inconcert with that by Rab8 and Rab11, which modulate the internalization and recycling ofmGlu1, respectively. TFR1 canbind to Rab proteins and facilitate their expression at synapses. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-LTP and PC intrinsic excitability are not affected. Finally, we demonstrate that PC ablation of TFR1 impairs motor coordination, but does not affect social behaviors in mice. Together, these findings underscore the importance of TFR1 in regulating mGlu1 trafficking and suggest that mGlu1-and mGlu1-dependent parallel fiber-LTD are associated with regulation of motor coordination, but not autistic behaviors.
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