title: The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania.
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 delta subunit of the adaptor protein 3 (AP3 delta) 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.
authors.affiliation: Wellcome Centre for Molecular Parasitology and Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, 120 University Place, Glasgow, G12 8TA, UK.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Besteiro
authors.forename: Daniela
authors.initials: D
authors.lastname: Tonn
authors.forename: Laurence
authors.initials: L
authors.lastname: Tetley
authors.forename: Graham H
authors.initials: GH
authors.lastname: Coombs
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Mottram
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D007891:Leishmania / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism*; D010758:Phosphorus / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D017494:Proton Pumps / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D011755:Pyrophosphatases / Q000378:metabolism
chemical_list: D033963:Adaptor Protein Complex 3; D008565:Membrane Proteins; D017494:Proton Pumps; D015800:Protozoan Proteins; D010758:Phosphorus; D011755:Pyrophosphatases; D002118:Calcium