Abstract
The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium, the male gamete surface protein P48/45 is vital to this process. This protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. To identify the role of additional members of this family in Plasmodium fertilisation, we performed genetic and functional analysis on the five members of the 6-cys family that are transcribed during the gametocyte stage of P. berghei. This analysis revealed that in addition to P48/45, two members (P230 and P47) also play an essential role in the process of parasite fertilization. Mating studies between parasites lacking P230, P48/45 or P47 demonstrate that P230, like P48/45, is a male fertility factor, consistent with the previous demonstration of a protein complex containing both P48/45 and P230. In contrast, disruption of P47 results in a strong reduction of female fertility, while males remain unaffected. Further analysis revealed that gametes of mutants lacking expression of p48/45 or p230 or p47 are unable to either recognise or attach to each other. Disruption of the paralog of p230, p230p, also specifically expressed in gametocytes, had no observable effect on fertilization. These results indicate that the P. berghei 6-cys family contains a number of proteins that are either male or female specific ligands that play an important role in gamete recognition and/or attachment. The implications of low levels of fertilisation that exist even in the absence of these proteins, indicating alternative pathways of fertilisation, as well as positive selection acting on these proteins, are discussed in the context of targeting these proteins as transmission blocking vaccine candidates.
Highlights
Sexual reproduction is an obligate process in the Plasmodium life cycle and is required for transmission of the parasites between the vertebrate and mosquito hosts
In this study we show that two gamete proteins, one expressed on the surface of males, the other on the surface of females, have important roles in the mutual recognition and attachment of gametes
We provide evidence that these three 6-cys proteins are undergoing strong but different rates of positive selection, either as a consequence sexualselection driven by the competition between gametes or from natural selection exerted by the adaptive immune system of the host on proteins expressed in gametocytes
Summary
Sexual reproduction is an obligate process in the Plasmodium life cycle and is required for transmission of the parasites between the vertebrate and mosquito hosts. Successful fertilisation requires an ordered series of gamete-gamete interactions, the recognition of and adhesion to the female gamete by the motile male gamete, followed by a cascade of signalling events resulting from the fusion of the two gametes. Despite their fundamental importance, relatively little is known about gamete receptors/ligands and their involvement in the process of gamete interactions of eukaryotes [1,2], which is partly due to their rapid evolution and species-specific characteristics [3]. The surface location of members of PLoS Pathogens | www.plospathogens.org
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have