SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation. Issue 7 (2nd July 2016)

• Record Type: Journal Article
• Authors: Wei, Zong-Bo; Yuan, Ye-Feng; Jaouen, Florence; Ma, Mei-Sheng; Hao, Chan-Juan; Zhang, Zhe; Chen, Quan; Yuan, Zengqiang; Yu, Li; Beurrier, Corinne; Li, Wei
• Is Part Of: Autophagy. Volume 12:Issue 7(2016)
• Page Start: 1168
• Page End: 1179
• Publication Date: 2016-07-02
• Subjects: autophagy -- BECN1-ATG14-PIK3C3 complex -- dopaminergic neuron -- neurodegeneration -- Parkinson disease -- SLC35D3; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2016.1179402
• Languages: English
• ISSNs: 1554-8627

Abstract

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.