Three Members of the 6-cys Protein Family of Plasmodium Play a Role in Gamete Fertility
By M. V. van Dijk, Ben C. L. van Schaijk, Shahid M. Khan, Maaike van Dooren, J. Ramesar, Szymon Kaczanowski, G. van Gemert, H. Kroeze, H. Stunnenberg, W. Eling and 3 more. 2010
215 citations recorded by the source corpus.
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.
Subfields: Epidemiology, Immunology, Public Health, Environmental and Occupational Health
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Citations in the corpus
- N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity (2011, background): “1A) (6, 11, 36) and elicits a humoral immune response in infected individuals that can mediate transmission-blocking immunity (12, 16).”
- Structure of the Plasmodium 6-cysteine s48/45 domain (2012, background): “falciparum, greatly reduces fertilization in the mosquito (11, 21).”
- Structure of the Pf12 and Pf41 heterodimeric complex of Plasmodium falciparum 6-cysteine proteins (2022, background): “The members of the 6-cysteine (6-cys) protein family represent some of the more abundant surface proteins and have crucial roles in hostcell entry, parasite sexual development and immune evasion strategies (1-5).”
- The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle (2016, methodology): “P12p was reported to be transcribed in the blood stages in P. falciparum by microarray and in P. berghei by northern blot analysis (Gilson et al., 2006; van Dijk et al., 2010).”
- Worldwide sequence conservation of transmission-blocking vaccine candidate Pvs230 in Plasmodium vivax (2011, background): “Genes for gametocytes/gamete surface proteins of rodent malaria parasites are rapidly evolving [19].”
- Transmission-Blocking Vaccines: Harnessing Herd Immunity for Malaria Elimination (2021, unknown): “berghei impairs male gamete fertility [34,35].”
- Identification of domains within Pfs230 that elicit transmission blocking antibody responses (2019, background): “berghei indicated that P230 played an important role in male gamete fertility [6].”