title: SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation.
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.
authors.affiliation: a State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Zong-Bo
authors.initials: ZB
authors.lastname: Wei
authors.affiliation: a State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Ye-Feng
authors.initials: YF
authors.lastname: Yuan
authors.affiliation: c Aix-Marseille University, Center National de la Recherche Scientifique , UMR 7288 , Institut de Biologie du Développement de Marseille, Marseille , France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jaouen
authors.affiliation: d School of Life Sciences, Tsinghua University , Beijing , China.
authors.forename: Mei-Sheng
authors.initials: MS
authors.lastname: Ma
authors.affiliation: a State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing , China.|e Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing Pediatric Research Institute , Beijing , China.
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Hao
authors.affiliation: a State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: f Institute of Zoology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: g Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: d School of Life Sciences, Tsinghua University , Beijing , China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: c Aix-Marseille University, Center National de la Recherche Scientifique , UMR 7288 , Institut de Biologie du Développement de Marseille, Marseille , France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Beurrier
authors.affiliation: a State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing , China.|e Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing Pediatric Research Institute , Beijing , China.|h Center of Alzheimer Disease, Beijing Institute for Brain Disorders , Beijing , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D000071186:Beclin-1 / Q000378:metabolism*; D058546:Class III Phosphatidylinositol 3-Kinases; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C561107:Atg14 protein, mouse; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D009004:Monosaccharide Transport Proteins; C518133:Slc35d3 protein, mouse; D033921:Vesicular Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D019869:Phosphatidylinositol 3-Kinases; D058546:Class III Phosphatidylinositol 3-Kinases; C000611846:PIK3C3 protein, mouse; D004298:Dopamine
keywords: BECN1-ATG14-PIK3C3 complex; Parkinson disease; SLC35D3; autophagy; dopaminergic neuron; neurodegeneration