Leishmaniacell surface prohibitin: role in host-parasite interaction

Abstract

SummaryProteins selectively upregulated in infective parasitic forms could be critical for disease pathogenesis. A mammalian prohibitin orthologue is upregulated in infective metacyclic promastigotes of Leishmania donovani, a parasite that causes visceral leishmaniasis. Leishmania donovani prohibitin shares 41% similarity with mammalian prohibitin and 95-100% within the genus. Prohibitin is concentrated at the surface of the flagellar and the aflagellar pole, the aflagellar pole being a region through which host-parasite interactions occur. Prohibitin is attached to the membrane through a GPI anchor. Overexpression of wild-type prohibitin increases protein surface density resulting in parasites with higher infectivity. However, parasites overexpressing a mutant prohibitin with an amino acid substitution at the GPI anchor site to prevent surface expression through GPI-link show lesser surface expression and lower infective abilities. Furthermore, the presence of anti-prohibitin antibodies during macrophage-Leishmania interaction in vitro reduces infection. The cognate binding partner for Leishmania prohibitin on the host cell appears to be macrophage surface HSP70, siRNA mediated downregulation of which abrogates the capability of the macrophage to bind to parasites. Leishmania prohibitin is able to generate a strong humoral response in visceral leishmaniasis patients. The above observations suggest that prohibitin plays an important role in events leading to Leishmania-host interaction.

Moving from unsequenced to sequenced genome: Reanalysis of the proteome of Leishmania donovani

“…The aflagellar pole is involved in invasion process of macrophage and it involves binding of prohibitin to its corresponding surface HSP70 receptor on macrophage. Hence, it seems to play an important role in host–parasite interaction [56]. Magnesium transporter 2 (MGT2) is a cation transporter encoded by the gene LDBPK_251130 and it is involved in the transport of magnesium in intracellular amastigotes engulfed in phogolysosome of macrophages.…”

Paromomycin Affects Translation and Vesicle-Mediated Trafficking as Revealed by Proteomics of Paromomycin –Susceptible –Resistant Leishmania donovani

“…Another protein, prohibitin, showed decreased protein expression levels (∼2.5 fold) in the PRr resistant strain. Prohibitin has been reported to play an important role in the events leading to Leishmania- host interaction [28]. Its homolog has been studied in Trypanosoma brucei and has been reported to be upregulated upon induction of apoptosis [29].…”

“…Another protein, prohibitin was also found to interact with PR. Prohibitin in Leishmania is reported to be concentrated at the surface of the flagellar and the aflagellar pole [28]. The flagellar pocket membrane is the only part of the cell surface that supports endocytosis and exocytosis [41].…”

“…Paraflagellar rod proteins and prohibitin were found to interact with paromomycin. Prohibitin in Leishmania is also reported to be concentrated at the surface of the flagellar and the aflagellar pole [28]. It is well known that the flagellar pocket facilitates internalization of the molecules.…”

Catalysis by N-Acetyl-d-glucosaminylphosphatidylinositol De-N-acetylase (PIG-L) from Entamoeba histolytica

“…GPI-anchored proteins are known to be involved in infection and virulence of many eukaryotic pathogens, including Trypanosoma, Leishmania, Candida, and Entamoeba (1)(2)(3)(4).…”