title: Uncovering the role of Snapin in regulating autophagy-lysosomal function.
abstract: The autophagy-lysosomal system is the major degradation pathway essential for the maintenance and survival of neurons. This process requires efficient late endocytic transport from distal processes to the soma, in which lysosomes are predominantly localized. However, it is not clear how late endocytic transport has an impact upon neuronal autophagy-lysosomal function. We recently revealed that Snapin acts as a dynein motor adaptor and coordinates retrograde transport and late endosomal-lysosomal trafficking, thus maintaining efficient autophagy-lysosomal function in neurons. Snapin(-/-) neurons display impaired retrograde transport and clustering of late endosomes along neuronal processes, aberrant accumulation of immature lysosomes, and impaired clearance of autolysosomes. Snapin deficiency leads to reduced neuron viability, neurodegeneration, and developmental defects in the central nervous system. Reintroducing the snapin transgene rescues these phenotypes by enhancing the delivery of endosomal cargos to lysosomes and by facilitating autophagy-lysosomal function. Our study suggests that Snapin is a candidate molecular target for autophagy-lysosomal regulation.
authors.affiliation: Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.forename: Zu-Hang
authors.initials: ZH
authors.lastname: Sheng
mesh_terms: D000818:Animals; D001343:Autophagy; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D008247:Lysosomes / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C118519:SNAPIN protein, human; D033921:Vesicular Transport Proteins