Actin-interacting and flagellar proteins in Leishmania spp.: bioinformatics predictions to functional assignments in phagosome formation

Abstract

Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented.

Identification, Localization, and Functional Implications of the Microdomain-Forming Stomatin Family in the Ciliated Protozoan Paramecium tetraurelia

“…Alternatively, the vacuole-bound protein vacuolin was described as being more closely related to Reggie/ Flotillin (59). In the parasitic flagellate Leishmania, Stomatin-like proteins (Sto-LPs) have been found, but functional evidence is scarce (64). The species closest to Paramecium endowed with a Stomatin ortholog is the malaria parasite, Plasmodium falciparum, which, together with ciliates, belongs to the phylum Alveolata.…”

Imaging Host Cell-Leishmania Interaction Dynamics Implicates Parasite Motility, Lysosome Recruitment, and Host Cell Wounding in the Infection Process

“…Various flagellar properties may contribute to parasite uptake. First, the particular composition of the trypanosomatid flagellar membrane highly enriched in lipid raft domains and specific components such as actin-interacting proteins might be associated with specialized functions of this organelle in adhesion and signaling (Diniz et al, 2009;Tyler et al, 2009). It is possible to speculate that specific capping of certain adhesiotopes at the flagellar tip of Leishmania parasite, such as LPG, gp63, or other surface molecules, might account for oriented attachment and entry of the parasite into BMMs through receptor/ligand interactions (Singla and Vinayak, 1994).…”

Evolutionary comparison of prenylation pathway in kinetoplastid Leishmania and its sister Leptomonas

“…Evolutionary distance of the lineage requires experimental evidence to further support these sequence data. It has been established by Diniz et al [ 27 ]: that Rab2 and Rab11B (which we now identify to be isoform of Rab2A) are actin interacting proteins (AIP) in L. infantum and L. major .…”