Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules

Suprabha Pulipparacharuvil, Mohammed Ali Akbar, Sanchali Ray, Evgueny A. Sevrioukov, Adam S. Haberman, Jack Rohrer, Helmut Krämer

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

Mutations that disrupt trafficking to lysosomes and lysosome-related organelles cause multiple diseases, including Hermansky-Pudlak syndrome. The Drosophila eye is a model system for analyzing such mutations. The eye-color genes carnation and deep orange encode two subunits of the Vps-C protein complex required for endosomal trafficking and pigment-granule biogenesis. Here we demonstrate that dVps16A (CG8454) encodes another Vps-C subunit. Biochemical experiments revealed a specific interaction between the dVps16A C-terminus and the Sec1/Munc18 homolog Carnation but not its closest homolog, dVps33B. Instead, dVps33B interacted with a related protein, dVps16B (CG18112). Deep orange bound both Vps16 homologs. Like a deep orange null mutation, eye-specific RNAi-induced knockdown of dVps16A inhibited lysosomal delivery of internalized ligands and interfered with biogenesis of pigment granules. Ubiquitous knockdown of dVps16A was lethal. Together, these findings demonstrate that Drosophila Vps16A is essential for lysosomal trafficking. Furthermore, metazoans have two types of Vps-C complexes with non-redundant functions.

Original languageEnglish (US)
Pages (from-to)3663-3673
Number of pages11
JournalJournal of cell science
Volume118
Issue number16
DOIs
StatePublished - Aug 15 2005

Keywords

  • Autophagosomes
  • Endocytic trafficking
  • Lysosome-related organelles
  • Pigment granules
  • Vps-C genes

ASJC Scopus subject areas

  • Cell Biology

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    Pulipparacharuvil, S., Akbar, M. A., Ray, S., Sevrioukov, E. A., Haberman, A. S., Rohrer, J., & Krämer, H. (2005). Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules. Journal of cell science, 118(16), 3663-3673. https://doi.org/10.1242/jcs.02502