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SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation |
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| Authors: | Zong-Bo Wei Ye-Feng Yuan Florence Jaouen Mei-Sheng Ma Chan-Juan Hao Zhe Zhang |
| Institution: | 1. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China;2. University of Chinese Academy of Sciences, Beijing, China;3. Aix-Marseille University, Center National de la Recherche Scientifique, UMR 7288, Institut de Biologie du Développement de Marseille, Marseille, France;4. School of Life Sciences, Tsinghua University, Beijing, China;5. Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing Pediatric Research Institute, Beijing, China |
| Abstract: | Searching for new regulators of autophagy involved in selective dopaminergic (DA) neuron loss is a hallmark in the pathogenesis of Parkinson disease (PD). We here report that an endoplasmic reticulum (ER)-associated transmembrane protein SLC35D3 is selectively expressed in subsets of midbrain DA neurons in about 10% TH (tyrosine hydroxylase)-positive neurons in the substantia nigra pars compacta (SNc) and in about 22% TH-positive neurons in the ventral tegmental area (VTA). Loss of SLC35D3 in ros (roswell mutant) mice showed a reduction of 11.9% DA neurons in the SNc and 15.5% DA neuron loss in the VTA with impaired autophagy. We determined that SLC35D3 enhanced the formation of the BECN1-ATG14-PIK3C3 complex to induce autophagy. These results suggest that SLC35D3 is a new regulator of tissue-specific autophagy and plays an important role in the increased autophagic activity required for the survival of subsets of DA neurons. |
| Keywords: | autophagy BECN1-ATG14-PIK3C3 complex dopaminergic neuron neurodegeneration Parkinson disease SLC35D3 |