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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.
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https://hal.archives-ouvertes.fr/hal-03079432
Contributor : Corinne Beurrier Connect in order to contact the contributor
Submitted on : Thursday, December 17, 2020 - 11:16:24 AM
Last modification on : Wednesday, November 17, 2021 - 12:31:10 PM

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Zong-Bo Wei, Ye-Feng Yuan, Florence Jaouen, Mei-Sheng Ma, Chan-Juan Hao, et al.. SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation. Autophagy, Taylor & Francis, 2016, 12 (7), pp.1168-1179. ⟨10.1080/15548627.2016.1179402⟩. ⟨hal-03079432⟩

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