Stage-specific expression of the proline-alanine transporter in the human pathogen Leishmania

• Published in: Molecular and biochemical parasitology 2018-06, Vol.222, p.1-5
• Main Authors: Liburkin-Dan, T., Schlisselberg, D., Fischer-Weinberger, R., Pescher, P., Inbar, E., Ephros, M., Rentsch, D., Späth, G.F., Zilberstein, D.
• Format: Article
• Language: English
• Subjects: Alanine; Alanine - metabolism; Amino acid transport; Amino Acid Transport Systems, Neutral; Amino Acid Transport Systems, Neutral - genetics; Amino Acid Transport Systems, Neutral - metabolism; Animals; Differentiation; Humans; Insect Vectors; Insect Vectors - parasitology; Leishmania; Leishmania donovani; Leishmania donovani - genetics; Leishmania donovani - growth & development; Leishmania donovani - metabolism; Leishmaniasis, Visceral; Leishmaniasis, Visceral - parasitology; Life Sciences; Lysosomes; Lysosomes - metabolism; Phlebotomus; Phlebotomus - parasitology; Proline; Proline - metabolism; Proteasome Endopeptidase Complex; Proteasome Endopeptidase Complex - metabolism; Protein degradation; Proteolysis; Protozoan Proteins; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Signal; Species Specificity; Stage-Specific expression
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/j.molbiopara.2018.04.002

•LdAAP24 is a transporter on the plasma membrane of Leishmania donovani.•Promastigotes express two variants that translocate proline and alanine.•Amastigotes, either axenic or intracellular do not express LdAAP24.•Inducing differentiation in axenic conditions activate rapid degradation of LdAAP24.•Differentiation-induced protein degradation had no effect on LdAAP24 mRNA. Leishmania are obligatory intracellular parasites that cycle between the sand fly midgut (extracellular promastigotes) and mammalian macrophage phagolysosomes (intracellular amastigotes). They have developed mechanisms of adaptation to the distinct environments of host and vector that favor utilization of both proline and alanine. LdAAP24 is the L. donovani proline-alanine transporter. It is a member of Leishmania system A that translocates neutral amino acids. Since system A is promastigote-specific, we aimed to assess whether LdAAP24 is also expressed exclusively in promastigotes. Herein, we established that upon exposing L. donovani promastigotes to amastigote differentiation signal (pH 5.5 and 37 °C), parasites rapidly and completely degrade LdAAP24 protein in both axenic and in spleen-derived amastigotes. In contrast, LdAAP24 mRNA remained unchanged throughout differentiation. Addition of either MG132 or Bafilomycin A1 partially inhibited LdAAP24 protein degradation, indicating a role for both lysosome- and proteasome-mediated degradation. This work provides the first evidence for post-translational regulation of stage-specific expression of LdAAP24.