BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon.
The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.
Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Ginny G
GG
Farías
Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Carlos M
CM
Guardia
Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Raffaella
R
De Pace
Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Dylan J
DJ
Britt
Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 juan.bonifacino@nih.gov.
Juan S
JS
Bonifacino
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D055647:Rats, Transgenic; D014157:Transcription Factors / Q000378:metabolism
D046912:Multiprotein Complexes; C581694:SKIP protein, rat; D014157:Transcription Factors; D016547:Kinesins; D020727:ADP-Ribosylation Factors
BORC; autophagosomes; kinesin-1; lysosomes; polarized organelle transport