Human Vam6p promotes lysosome clustering and fusion in vivo

Steve Caplan, Lisa M. Hartnell, Rubén C. Aguilar, Naava Naslavsky, Juan S. Bonifacino

Research output: Contribution to journalArticle

113 Citations (Scopus)

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 NH2 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 μm) 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.

Original languageEnglish (US)
Pages (from-to)109-121
Number of pages13
JournalJournal of Cell Biology
Volume154
Issue number1
DOIs
StatePublished - Jul 9 2001

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Lysosomes
Cluster Analysis
Clathrin Heavy Chains
Proteins
Saccharomyces cerevisiae Proteins
Endosomes
Protein Transport

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Human Vam6p promotes lysosome clustering and fusion in vivo. / Caplan, Steve; Hartnell, Lisa M.; Aguilar, Rubén C.; Naslavsky, Naava; Bonifacino, Juan S.

In: Journal of Cell Biology, Vol. 154, No. 1, 09.07.2001, p. 109-121.

Research output: Contribution to journalArticle

Caplan, Steve ; Hartnell, Lisa M. ; Aguilar, Rubén C. ; Naslavsky, Naava ; Bonifacino, Juan S. / Human Vam6p promotes lysosome clustering and fusion in vivo. In: Journal of Cell Biology. 2001 ; Vol. 154, No. 1. pp. 109-121.
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