SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation
- Autophagy. 2016 Jul 2;12(7):1168-79. doi: 10.1080/15548627.2016.1179402.
- 1. a State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing , China.
- 2. b University of Chinese Academy of Sciences , Beijing , China.
- 3. c Aix-Marseille University, Center National de la Recherche Scientifique , UMR 7288 , Institut de Biologie du Développement de Marseille, Marseille , France.
- 4. d School of Life Sciences, Tsinghua University , Beijing , China.
- 5. e Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing Pediatric Research Institute , Beijing , China.
- 6. f Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
- 7. g Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
- 8. h Center of Alzheimer Disease, Beijing Institute for Brain Disorders , Beijing , China.
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.