Drosophila mauve mutants reveal a role of LYST homologs late in the maturation of phagosomes and autophagosomes

Mokhlasur Rahman, Adam Haberman, Charles Tracy, Sanchali Ray, Helmut Krämer

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Chediak-Higashi syndrome (CHS) is a lethal disease caused by mutations that inactivate the lysosomal trafficking regulator protein (LYST). Patients suffer from diverse symptoms including oculocutaneous albinism, recurrent infections, neutropenia and progressive neurodegeneration. These defects have been traced back to over-sized lysosomes and lysosome-related organelles (LROs) in different cell types. Here, we explore mutants in the Drosophila mauve gene as a new model system for CHS. The mauve gene (CG42863) encodes a large BEACH domain protein of 3535 amino acids similar to LYST. This reflects a functional homology between these proteins as mauve mutants also display enlarged LROs, such as pigment granules. This Drosophila model also replicates the enhanced susceptibility to infections and we show a defect in the cellular immune response. Early stages of phagocytosis proceed normally in mauve mutant hemocytes but, unlike in wild type, late phagosomes fuse and generate large vacuoles containing many bacteria. Autophagy is similarly affected in mauve fat bodies as starvation-induced autophagosomes grow beyond their normal size. Together these data suggest a model in which Mauve functions to restrict homotypic fusion of different pre-lysosomal organelles and LROs.

Original languageEnglish (US)
Pages (from-to)1680-1692
Number of pages13
JournalTraffic
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2012

    Fingerprint

Keywords

  • Autophagy
  • Chediak-Higashi syndrome
  • Hemocytes
  • Lysosome-related organelles
  • Phagocytosis
  • Pigment granules

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this