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.

Atg5- and Atg7-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to morphine

“…A recent study showed that SLC35D3 (solute carrier family 35, member D3), as a regulator of tissuespecific autophagy, increases autophagic activity in midbrain dopaminergic neurons via enhancing BECN1-ATG14-PIK3C3 complex formation. 42 It would be rewarding to test whether this process was also involved in the morphine-induced dopaminergic neuron-specific autophagy in the midbrain.…”

Oxidized low‐density lipoprotein induced mouse hippocampal HT‐22 cell damage via promoting the shift from autophagy to apoptosis

“…Many studies have indicated that disrupted autophagy flux contributes to neuronal cell injury and death in brain of patients with neurodegenerative diseases, including amyotrophic lateral sclerosis, PD‐like dementia, and Huntington's disease . Thus, we next investigated whether autophagy implicated in ox‐LDL‐induced HT‐22 cell injury and apoptosis.…”

Molecular cloning, sequence characteristics, and tissue expression analysis of the SLC35D3 gene in lean, obese and mini-type pigs

“…Recent research indicates that SLC35D3 is involved in the biogenesis of platelet dense granules, and the expression of SLC35D3 in the brain was limited to expressing D1R rather than D2R [20][21][22]. Other 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 [23]. Moreover, reports on the expression and structure of the SLC35D3 gene are not available in swine [24].…”