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BORC, a Multisubunit Complex that Regulates Lysosome Positioning

Thursday, September 17, 2015 — Poster Session III

3:30 p.m. – 5:00 p.m.
FAES Terrace
NICHD
CELLBIO-15

* FARE Award Winner

Authors

  • J Pu
  • C Schindler
  • R Jia
  • M Jarnik
  • P Backlund
  • JS Bonifacino

Abstract

The positioning of lysosomes within the cytoplasm is emerging as a critical determinant of many lysosomal functions. Herein we report the identification of a multisubunit complex named BORC that regulates lysosome positioning. BORC comprises eight subunits, of which some are shared with the BLOC-1 complex involved in the biogenesis of lysosome-related organelles and the others are products of previously uncharacterized open reading frames. BORC peripherally associates with the lysosomal membrane, where it functions to recruit the small GTPase Arl8. This initiates a chain of interactions that promotes Kinesin-1-dependent movement of lysosomes towards 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.

Category: Cell Biology