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

Sébastien Besteiro, Daniela Tonn, L. Tetley, G.H. Coombs, J.C. Mottram

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44 Citations (Scopus)

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 subunit of the adaptor protein 3 (AP3 ) 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.
Original languageEnglish
Pages (from-to)561-570
Number of pages9
JournalJournal of Cell Science
Volume121
DOIs
Publication statusPublished - 2008

Keywords

  • adaptor protein
  • AP3
  • acidocalcisomes
  • membrane-protein transport
  • Leishmania

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