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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | De Zeeuw, Chris I. Xie, Ya-jun Li, Hua-shun Han, Shuo Zhou, Liang Yang, Dong Zhou, Jia-huan Qiu, Meng-sheng Wang, De-juan Zhou, Lin Zhu, J. Julius Shen, Ying Huang, Hao Shao, Chong-yu |
| Description | Author Affiliation: Zhou L ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Yang D ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Wang DJ ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Xie YJ ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Zhou JH ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Zhou L ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Huang H ( Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Hangzhou 310029, China); Han S ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Shao CY ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); Li HS ( SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China); Zhu JJ ( Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville, VA 22908); Qiu MS ( Institute of Developmental and Regenerative Biology, College of Life and Environmental Science, Hangzhou Normal University, Hangzhou 310029, China); De Zeeuw CI ( Department of Neuroscience, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands); Shen Y ( Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang University School of Medicine, Hangzhou 310058, China); |
| Abstract | Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro. Nevertheless, its function in mature neurons has not yet been elucidated. Here we show that cerebellar Purkinje cells (PCs) express high levels of Numb during adulthood and that conditional deletion of Numb in PCs is sufficient to impair motor coordination despite maintenance of a normal cerebellar cyto-architecture. Numb proved to be critical for internalization and recycling of metabotropic glutamate 1 receptor (mGlu1) in PCs. A significant decrease of mGlu1 and an inhibition of long-term depression at the parallel fiber-PC synapse were observed in conditional Numb knockout mice. Indeed, the trafficking of mGlu1 induced by agonists was inhibited significantly in these mutants, but the expression of ionotropic glutamate receptor subunits and of mGlu1-associated proteins was not affected by the loss of Numb. Moreover, transient and persistent forms of mGlu1 plasticity were robustly induced in mutant PCs, suggesting that they do not require mGlu1 trafficking. Together, our data demonstrate that Numb is a regulator for constitutive expression and dynamic transport of mGlu1. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cerebellum Metabolism Membrane Proteins Deficiency Motor Activity Nerve Tissue Proteins Purkinje Cells Receptors, Metabotropic Glutamate Synapses Animals Drug Effects Growth & Development Long-Term Potentiation Long-Term Synaptic Depression Membrane Potentials Methoxyhydroxyphenylglycol Analogs & Derivatives Pharmacology Mice, Knockout Morphogenesis Patch-Clamp Techniques Cytology Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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