Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology

Dingyin Tao, Ceereena Ubaida-Mohien, Derrick K. Mathias, Jonas G. King, Rebecca Pastrana-Mena, Abhai Tripathi, Ilana Goldowitz, David Graham, Eli Moss, Matthias Marti, Rhoel R. Dinglasan

Research output: Contribution to journalArticle

Abstract

One of the critical gaps in malaria transmission biology and surveillance is our lack of knowledge about Plasmodium falciparum gametocyte biology, especially sexual dimorphic development and how sex ratios that may influence transmission from the human to the mosquito. Dissecting this process has been hampered by the lack of sex-specific protein markers for the circulating, mature stage V gametocytes. The current evidence suggests a high degree of conservation in gametocyte gene complement across Plasmodium, and therefore presumably for sex-specific genes as well. To better our understanding of gametocyte development and subsequent infectiousness to mosquitoes, we undertook a Systematic Subtractive Bioinformatic analysis (filtering) approach to identify sexspecific P. falciparum NF54 protein markers based on a comparison with the Dd2 strain, which is defective in producing males, and with syntenic male and female proteins from the reanalyzed and updated P. berghei (related rodent malaria parasite) gametocyte proteomes. This produced a short list of 174 male- and 258 female-enriched P. falciparum stage V proteins, some of which appear to be under strong diversifying selection, suggesting ongoing adaptation to mosquito vector species. We generated antibodies against three putative female-specific gametocyte stage V proteins in P. falciparum and confirmed either conserved sex-specificity or the lack of crossspecies sex-partitioning. Finally, our study provides not only an additional resource for mass spectrometry-derived evidence for gametocyte proteins but also lays down the foundation for rational screening and development of novel sex-partitioned protein biomarkers and transmission-blocking vaccine candidates.

Original languageEnglish (US)
Pages (from-to)2705-2724
Number of pages20
JournalMolecular and Cellular Proteomics
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2014

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Cytology
Proteome
Plasmodium falciparum
Cell Biology
Proteins
Sexual Development
Culicidae
Malaria
Genes
Plasmodium
Sex Ratio
Biomarkers
Bioinformatics
Computational Biology
Mass spectrometry
Rodentia
Conservation
Mass Spectrometry
Screening
Parasites

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry
  • Medicine(all)

Cite this

Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology. / Tao, Dingyin; Ubaida-Mohien, Ceereena; Mathias, Derrick K.; King, Jonas G.; Pastrana-Mena, Rebecca; Tripathi, Abhai; Goldowitz, Ilana; Graham, David; Moss, Eli; Marti, Matthias; Dinglasan, Rhoel R.

In: Molecular and Cellular Proteomics, Vol. 13, No. 10, 01.10.2014, p. 2705-2724.

Research output: Contribution to journalArticle

Tao, D, Ubaida-Mohien, C, Mathias, DK, King, JG, Pastrana-Mena, R, Tripathi, A, Goldowitz, I, Graham, D, Moss, E, Marti, M & Dinglasan, RR 2014, 'Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology', Molecular and Cellular Proteomics, vol. 13, no. 10, pp. 2705-2724. https://doi.org/10.1074/mcp.M114.040956
Tao, Dingyin ; Ubaida-Mohien, Ceereena ; Mathias, Derrick K. ; King, Jonas G. ; Pastrana-Mena, Rebecca ; Tripathi, Abhai ; Goldowitz, Ilana ; Graham, David ; Moss, Eli ; Marti, Matthias ; Dinglasan, Rhoel R. / Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology. In: Molecular and Cellular Proteomics. 2014 ; Vol. 13, No. 10. pp. 2705-2724.
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