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Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major

Besteiro, S. and Williams, R.A. and Morrison, L.S. and Coombs, G.H. and Mottram, J.C. (2006) Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major. Journal of Biological Chemistry, 281 (16). pp. 11384-11396. ISSN 0021-9258

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Abstract

Cellular remodeling during differentiation is essential for lifecycle progression of many unicellular eukaryotic pathogens such as Leishmania, but the mechanisms involved are largely uncharacterized. The role of endosomal sorting in differentiation was analyzed in Leishmania major by overexpression of a dominant-negative ATPase, VPS4. VPS4E235Q accumulated in vesicles from the endocytic pathway, and the mutant L. major was deficient in endosome sorting. Mutant parasites failed to differentiate to the obligate infective metacyclic promastigote form. Furthermore, the autophagy pathway, monitored via the expression of autophagosome marker GFP-ATG8, and shown to normally peak during initiation of metacyclogenesis, was disrupted in the mutants. The defect in late endosome-autophagosome function in the VPS4E235Q parasites made them less able to withstand starvation than wild-type L. major. In addition, a L. major ATG4-deficient mutant was found also to be defective in the ability to differentiate. This finding, that transformation to the infective metacyclic form is dependent on late endosome function and, more directly, autophagy, makes L. major a good model for studying the roles of these processes in differentiation.

Item type: Article
ID code: 10509
Keywords: developmental biology, endosome sorting, autophagy, Leishmania major, Pharmacy and materia medica, Biochemistry, Cell Biology, Molecular Biology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 21 Apr 2011 05:04
    Last modified: 04 Sep 2014 19:57
    URI: http://strathprints.strath.ac.uk/id/eprint/10509

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