HPS6 interacts with dynactin p150Glued to mediate retrograde trafficking and maturation of lysosomes

J Cell Sci. 2014 Nov 1;127(Pt 21):4574-88. doi: 10.1242/jcs.141978. Epub 2014 Sep 4.


Hermansky-Pudlak syndrome 6 protein (HPS6) has originally been identified as a subunit of the BLOC-2 protein complex that is involved in the biogenesis of lysosome-related organelles. Here, we demonstrate that HPS6 directly interacts with the dynactin p150(Glued) subunit of the dynein-dynactin motor complex and acts as cargo adaptor for the retrograde motor to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Small interfering RNA (siRNA)-mediated knockdown of HPS6 in HeLa cells not only partially blocks centripetal movement of lysosomes but also causes delay in lysosome-mediated protein degradation. Moreover, lysosomal acidification and degradative capacity, as well as fusion between late endosomes and/or multivesicular bodies and lysosomes are also impaired when HPS6 is depleted, suggesting that perinuclear positioning mediated by the dynein-dynactin motor complex is required for lysosome maturation and activity. Our results have uncovered a so-far-unknown specific role for HPS6 in the spatial distribution of the lysosomal compartment.

Keywords: DCTN1; HPS6; dynein–dynactin motor complex; lysosome; p150Glued.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Dynactin Complex
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lysosomes / metabolism*
  • Mice
  • Microscopy, Confocal
  • Microtubule-Associated Proteins / metabolism*
  • Mutation
  • Protein Binding
  • Protein Transport / physiology
  • Two-Hybrid System Techniques


  • DCTN1 protein, human
  • Dctn1 protein, mouse
  • Dynactin Complex
  • HPS6 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins