Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes. 2015

Xiu-Tang Cheng, and Bing Zhou, and Mei-Yao Lin, and Qian Cai, and Zu-Hang Sheng
The Joint PhD program of the National Institutes of Health-Shanghai Jiao Tong University School of Medicine, Basic Medical Faculty, Shanghai Jiao Tong University School of Medicine, Shanghai, China 200025 Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Efficient degradation of autophagic vacuoles (AVs) via lysosomes is an important cellular homeostatic process. This is particularly challenging for neurons because mature acidic lysosomes are relatively enriched in the soma. Although dynein-driven retrograde transport of AVs was suggested, a fundamental question remains how autophagosomes generated at distal axons acquire dynein motors for retrograde transport toward the soma. In this paper, we demonstrate that late endosome (LE)-loaded dynein-snapin complexes drive AV retrograde transport in axons upon fusion of autophagosomes with LEs into amphisomes. Blocking the fusion with syntaxin17 knockdown reduced recruitment of dynein motors to AVs, thus immobilizing them in axons. Deficiency in dynein-snapin coupling impaired AV transport ,: resulting in AV accumulation in neurites and synaptic terminals. Altogether, our study provides the first evidence that autophagosomes recruit dynein through fusion with LEs and reveals a new motor-adaptor sharing mechanism by which neurons may remove distal AVs engulfing aggregated proteins and dysfunctional organelles for efficient degradation in the soma.

UI MeSH Term Description Entries
D010588 Phagosomes Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material. Phagolysosomes,Phagolysosome,Phagosome
D011992 Endosomes Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Receptosomes,Endosome,Receptosome
D004398 Dyneins A family of multi-subunit cytoskeletal motor proteins that use the energy of ATP hydrolysis, generated by a ring of AAA ATPASES in the dynein heavy chain, to power a variety of cellular functions. Dyneins fall into two major classes based upon structural and functional criteria. ATPase, Dynein,Adenosinetriphosphatase, Dynein,Dynein,Dynein ATPase,Dynein Adenosinetriphosphatase,Dynein Heavy Chain,Dynein Intermediate Chain,Dynein Light Chain,Dynein Light Intermediate Chain,Adenosine Triphosphatase, Dynein,Dynein Heavy Chains,Dynein Intermediate Chains,Dynein Light Chains,Dynein Light Intermediate Chains,Chain, Dynein Heavy,Chain, Dynein Intermediate,Chain, Dynein Light,Chains, Dynein Heavy,Chains, Dynein Intermediate,Chains, Dynein Light,Dynein Adenosine Triphosphatase,Heavy Chain, Dynein,Heavy Chains, Dynein,Intermediate Chain, Dynein,Intermediate Chains, Dynein,Light Chain, Dynein,Light Chains, Dynein
D005727 Ganglia, Spinal Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain. Dorsal Root Ganglia,Spinal Ganglia,Dorsal Root Ganglion,Ganglion, Spinal,Ganglia, Dorsal Root,Ganglion, Dorsal Root,Spinal Ganglion
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon
D001370 Axonal Transport The directed transport of ORGANELLES and molecules along nerve cell AXONS. Transport can be anterograde (from the cell body) or retrograde (toward the cell body). (Alberts et al., Molecular Biology of the Cell, 3d ed, pG3) Axoplasmic Flow,Axoplasmic Transport,Axoplasmic Streaming,Axonal Transports,Axoplasmic Flows,Axoplasmic Transports,Streaming, Axoplasmic,Transport, Axonal,Transport, Axoplasmic,Transports, Axonal,Transports, Axoplasmic
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D050765 Qa-SNARE Proteins A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES. Qa-SNAREs,Syntaxin,Syntaxin 10,Syntaxin 10 Protein,Syntaxin 11,Syntaxin 11 Protein,Syntaxin 13,Syntaxin 13 Protein,Syntaxin 17,Syntaxin 17 Protein,Syntaxin 18,Syntaxin 18 Protein,Syntaxin 1A Homologs,Syntaxin 3,Syntaxin 3 Protein,Syntaxin 3A,Syntaxin 3A Protein,Syntaxin 3B,Syntaxin 3B Protein,Syntaxin 3C,Syntaxin 3C Protein,Syntaxin 3D,Syntaxin 3D Protein,Syntaxin 4,Syntaxin 4 Protein,Syntaxin 5,Syntaxin 5 Protein,Syntaxin 6,Syntaxin 6 Protein,Syntaxin 7,Syntaxin 7 Protein,Syntaxin 8,Syntaxin 8 Protein,Syntaxin Protein,Syntaxin Proteins,Syntaxins,Protein, Syntaxin,Protein, Syntaxin 11,Proteins, Syntaxin,Qa SNARE Proteins,Qa SNAREs

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