Developmental Cell
Volume 33, Issue 2, 20 April 2015, Pages 176-188
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Article
BORC, a Multisubunit Complex that Regulates Lysosome Positioning

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Highlights

  • BORC is a multisubunit complex associated with the cytosolic face of lysosomes

  • BORC recruits Arl8, coupling lysosomes to microtubule plus-end-directed kinesin motor

  • BORC therefore promotes the movement of lysosomes toward the peripheral cytoplasm

  • BORC-dependent lysosome dispersal contributes to cell spreading and motility

Summary

The positioning of lysosomes within the cytoplasm is emerging as a critical determinant of many lysosomal functions. Here we report the identification of a multisubunit complex named BORC that regulates lysosome positioning. BORC comprises eight subunits, some of which are shared with the BLOC-1 complex involved in the biogenesis of lysosome-related organelles, and the others of which are products of previously uncharacterized open reading frames. BORC associates peripherally with the lysosomal membrane, where it functions to recruit the small GTPase Arl8. This initiates a chain of interactions that promotes the kinesin-dependent movement of lysosomes toward the plus ends of microtubules in the peripheral cytoplasm. Interference with BORC or other components of this pathway results in collapse of the lysosomal population into the pericentriolar region. In turn, this causes reduced cell spreading and migration, highlighting the importance of BORC-dependent centrifugal transport for non-degradative functions of lysosomes.

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