Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility.
Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility.
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DOI：
10.1371/journal.ppat.1000853
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发表时间：
2010-04-08
期刊：
影响因子：
6.7
通讯作者：
Janse CJ
中科院分区：
文献类型：
--
作者：
van Dijk MR;van Schaijk BC;Khan SM;van Dooren MW;Ramesar J;Kaczanowski S;van Gemert GJ;Kroeze H;Stunnenberg HG;Eling WM;Sauerwein RW;Waters AP;Janse CJ
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. Sexual reproduction for malaria parasites is an essential process and is necessary for parasite transmission between hosts. Fertilisation between female and male gametes occurs in the midgut of the mosquito and proteins on the surface of gametes are principle targets in transmission blocking strategies. Despite their importance, relatively little is known about the malaria proteins involved in fertilisation. 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. Mutant parasites that lack the presence of these surface proteins show a strong reduction in fertility. Comparison of these gamete surface proteins in different malaria parasites showed that these proteins are evolving rapidly either across their length or at discreet regions/domains. We found, that despite the drastic reduction in zygote formation, low levels of fertilisation can still occur in the absence of these surface proteins, indicating that gametes can use alternative proteins to recognize each other. Both genetic variation of gamete surface proteins and the presence of different fertilisation pathways have important implications for transmission blocking vaccines targeting gamete surface proteins.
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