2. Academic Validation
  3. SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation

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.
Zong-Bo Wei 1 2,  Ye-Feng Yuan 1 2,  Florence Jaouen 3,  Mei-Sheng Ma 4,  Chan-Juan Hao 1 5,  Zhe Zhang 1,  Quan Chen 6,  Zengqiang Yuan 7,  Li Yu 4,  Corinne Beurrier 3,  Wei Li 1 5 8
Affiliations

Affiliations

  • 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.
PMID: 27171858 DOI: 10.1080/15548627.2016.1179402
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

BECN1-ATG14-PIK3C3 complex; Parkinson disease; SLC35D3; autophagy; dopaminergic neuron; neurodegeneration.

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