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

Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):E2955-E2964. doi: 10.1073/pnas.1616363114. Epub 2017 Mar 20.

Abstract

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.

Keywords: BORC; autophagosomes; kinesin-1; lysosomes; polarized organelle transport.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • ADP-Ribosylation Factors / metabolism
  • Animals
  • Autophagosomes / metabolism
  • Axons / metabolism*
  • Biological Transport
  • Cells, Cultured
  • Dendrites / metabolism
  • Hippocampus / cytology
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Lysosomes / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Neurons / metabolism*
  • Rats
  • Rats, Transgenic
  • Transcription Factors / metabolism

Substances

  • Multiprotein Complexes
  • SKIP protein, rat
  • Transcription Factors
  • Kinesins
  • ADP-Ribosylation Factors