BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

被引:150
作者
Farias, Ginny G. [1 ]
Guardia, Carlos M. [1 ]
De Pace, Raffaella [1 ]
Britt, Dylan J. [1 ]
Bonifacino, Juan S. [1 ]
机构
[1] NIH, Cell Biol & Neurobiol Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA
关键词
lysosomes; polarized organelle transport; kinesin-1; BORC; autophagosomes; ARF-LIKE GTPASE; KINESIN HEAVY-CHAIN; POSTTRANSLATIONAL MODIFICATIONS; CAENORHABDITIS-ELEGANS; PREFERENTIAL BINDING; DEPENDENT EXOCYTOSIS; SPATIAL-DISTRIBUTION; SYMPATHETIC NEURONS; ALZHEIMERS-DISEASE; MOTOR PROTEINS;
D O I
10.1073/pnas.1616363114
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:E2955 / E2964
页数:10
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