Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut

Abstract

Physical contact is important for the interaction between animal cells, but can represent a major challenge for protists like malaria parasites. Recently, novel filamentous cell-cell contacts have been identified in different types of eukaryotic cells and termed nanotubes due to their morphological appearance. Nanotubes represent small dynamic membranous extensions that consist of F-actin and are considered an ancient feature evolved by eukaryotic cells to establish contact for communication. We here describe similar tubular structures in the malaria pathogen Plasmodium falciparum, which emerge from the surfaces of the forming gametes upon gametocyte activation in the mosquito midgut. The filaments can exhibit a length of more than 100 µm and contain the F-actin isoform actin 2. They actively form within a few minutes after gametocyte activation and persist until the zygote transforms into the ookinete. The filaments originate from the parasite plasma membrane, are close-ended and express adhesion proteins on their surfaces that are typically found in gametes, like Pfs230, Pfs48/45 or Pfs25, but not the zygote surface protein Pfs28. We show that these tubular structures represent long-distance cell-to-cell connections between sexual stage parasites and demonstrate that they meet the characteristics of nanotubes. We propose that malaria parasites utilize these adhesive “nanotubes” in order to facilitate intercellular contact between gametes during reproduction in the mosquito midgut.

The development of malaria parasites in the mosquito midgut

“…Hitherto, the fate of the alveoli during breakdown is unknown; noteworthy, the isochronal formation of nanotubes in the developing gametes was previously reported. Nanotubes are long membranous tubules that originate from the gamete surface and represent long‐distance cell‐to‐cell connections proposed to facilitate contact between gametes as a pre‐requisite for mating (Rupp et al ., 2011). While the question of the origin of the membranous tubules remains, one explanation might be that the alveolar membranes are reused for nanotube formation.…”

Malaria proteases mediate inside-out egress of gametocytes from red blood cells following parasite transmission to the mosquito

“…Homogenous surface expression of Pfs25 can only be observed in fully emerged PVM-negative macrogametes (E). Arrowheads indicate nanotubes (Rupp et al, 2011). Bar, 2 mm.…”

The languages of parasite communication

“…These filaments, which are derived from the plasma membrane, contain actin and are covered with gamete-specific proteins. Filament formation was observed in the mosquito midgut as well as in culture, indicating that it is a natural process, most probably to facilitate contact between gametes and subsequent fertilisation [56]. An unusual form of direct communication has recently been described for procyclic form trypanosomes [57].…”

“…Following activation of Plasmodium gametocytes, the parasites form closed, nanotubelike filaments that attach to the surface of other cells [56]. These filaments, which are derived from the plasma membrane, contain actin and are covered with gamete-specific proteins.…”