Human Vam6p promotes lysosome clustering and fusion in vivo

  • Caplan S
  • Hartnell L
  • Aguilar R
 et al. 
  • 66

    Readers

    Mendeley users who have this article in their library.
  • 110

    Citations

    Citations of this article.

Abstract

Regulated fusion of mammalian lysosomes is critical to their ability to acquire both internalized and biosynthetic materials. Here, we report the identification of a novel human protein, hVam6p, that promotes lysosome clustering and fusion in vivo. Although hVam6p exhibits homology to the Saccharomyces cerevisiae vacuolar protein sorting gene product Vam6p/Vps39p, the presence of a citron homology (CNH) domain at the NH(2) terminus is unique to the human protein. Overexpression of hVam6p results in massive clustering and fusion of lysosomes and late endosomes into large (2-3 microm) juxtanuclear structures. This effect is reminiscent of that caused by expression of a constitutively activated Rab7. However, hVam6p exerts its effect even in the presence of a dominant-negative Rab7, suggesting that it functions either downstream of, or in parallel to, Rab7. Data from gradient fractionation, two-hybrid, and coimmunoprecipitation analyses suggest that hVam6p is a homooligomer, and that its self-assembly is mediated by a clathrin heavy chain repeat domain in the middle of the protein. Both the CNH and clathrin heavy chain repeat domains are required for induction of lysosome clustering and fusion. This study implicates hVam6p as a mammalian tethering/docking factor characterized with intrinsic ability to promote lysosome fusion in vivo.

Author-supplied keywords

  • Lysosome biogenesis
  • Lysosome fusion
  • Vacuolar protein sorting
  • Vesicle docking
  • Vesicle tethering

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Juan S. BonifacinoNational Institute of Child Health and Human Development

    Follow
  • Steve Caplan

  • Lisa M. Hartnell

  • Rubén C. Aguilar

  • Naava Naslavsky

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free