Open AccessLeishmania Adaptor Protein-1 Subunits Are Required for Normal Lysosome Traffic, Flagellum Biogenesis, Lipid Homeostasis, and Adaptation to Temperatures Encountered in the Mammalian Host
Author(s) -
James E. Vince,
Dedreia Tull,
Timothy P. Spurck,
Merran C. Derby,
Geoffrey I. McFadden,
Paul A. Gleeson,
Suzanne Gokool,
Malcolm J. McConville
Publication year - 2008
Publication title -
eukaryotic cell
Language(s) - English
Resource type - Journals
eISSN - 1535-9778
pISSN - 1535-9786
DOI - 10.1128/ec.00090-08
Subject(s) - biology , endosome , microbiology and biotechnology , golgi apparatus , lysosome , endocytic cycle , signal transducing adaptor protein , lipophosphoglycan , transport protein , biogenesis , endomembrane system , leishmania mexicana , endocytosis , endoplasmic reticulum , leishmania , biochemistry , leishmania donovani , signal transduction , intracellular , genetics , gene , enzyme , parasite hosting , world wide web , computer science , cell , leishmaniasis , visceral leishmaniasis
The adaptor protein-1 (AP-1) complex is involved in membrane transport between the Golgi apparatus and endosomes. In the protozoan parasiteLeishmania mexicana mexicana , the AP-1 μ1 and σ1 subunits are not required for growth at 27°C but are essential for infectivity in the mammalian host. In this study, we have investigated the function of these AP-1 subunits in order to understand the molecular basis for this loss of virulence. The μ1 and σ1 subunits were localized to late Golgi and endosome membranes of the major parasite stages. Parasite mutants lacking either AP-1 subunit lacked obvious defects in Golgi structure, endocytosis, or exocytic transport. However, these mutants displayed reduced rates of endosome-to-lysosome transport and accumulated fragmented, sterol-rich lysosomes. Defects in flagellum biogenesis were also evident in nondividing promastigote stages, and this phenotype was exacerbated by inhibitors of sterol and sphingolipid biosynthesis. Furthermore, both AP-1 mutants were hypersensitive to elevated temperature and perturbations in membrane lipid composition. The pleiotropic requirements for AP-1 in membrane trafficking and temperature stress responses explain the loss of virulence of these mutants in the mammalian host.