The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania

Besteiro, S., Tonn, D., Tetley, L., Coombs, G. H. and Mottram, J. C. (2008) The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania. Journal of Cell Science, 121(5), pp. 561-570. (doi:10.1242/jcs.022574)

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Publisher's URL: http://dx.doi.org/10.1242/jcs.022574

Abstract

Lysosomal function is crucial for the differentiation and infectivity of the parasitic protozoon Leishmania major. To study lysosomal biogenesis, an L. major mutant deficient in the δ subunit of the adaptor protein 3 (AP3 δ) complex was generated. Structure and proteolytic capacity of the lysosomal compartment were apparently unaffected in the AP3-deficient mutant; however, defects were identified in its acidocalcisomes. These are acidic organelles enriched in calcium and phosphorus, conserved from bacteria to eukaryotes, whose function remains enigmatic. The acidocalcisomes of the L. major mutant lacked membrane-bound proton pumps (notably V-H+-PPase), were less acidic than normal acidocalcisomes and devoid of polyphosphate, but contained a soluble pyrophosphatase. The mutant parasites were viable in vitro, but were unable to establish an infection in mice, which indicates a role for AP3 in determining possibly through an acidocalcisome-related function the virulence of the parasite. AP3 transport function has been linked previously to lysosome-related organelles such as platelet dense granules, which appear to share several features with acidocalcisomes. Our findings, implicating that AP3 has a role in transport to acidocalcisomes, thus provide further evidence that biogenesis of acidocalcisomes resembles that of lysosome-related organelles, and that both may have conserved origins

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tetley, Dr Laurence and Mottram, Professor Jeremy
Authors: Besteiro, S., Tonn, D., Tetley, L., Coombs, G. H., and Mottram, J. C.
Subjects:Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Cell Science
Publisher:The Company of Biologists Ltd.
ISSN:0021-9533
ISSN (Online):1477-9137
Published Online:05 February 2008
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
297261Post-genomic analysis of cysteine protease function in Leishmania parasitesJeremy MottramMedical Research Council (MRC)G0000508Infection Immunity and Inflammation Life Sciences