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

Tao, D. et al. (2014) Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology. Molecular and Cellular Proteomics, 13(10), pp. 2705-2724. (doi: 10.1074/mcp.M114.040956) (PMID:25056935) (PMCID:PMC4188997)

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 sex-specific 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 cross-species 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Marti, Professor Matthias
• Authors: Tao, D., Ubaida-Mohien, C., Mathias, D. K., King, J. G., Pastrana-Mena, R., Tripathi, A., Goldowitz, I., Graham, D. R., Moss, E., Marti, M., and Dinglasan, R. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Molecular and Cellular Proteomics
• Publisher: American Society for Biochemistry and Molecular Biology
• ISSN: 1535-9476
• ISSN (Online): 1535-9484
• Published Online: 23 July 2014
• Copyright Holders: Copyright © 2014 The American Society for Biochemistry and Molecular Biology, Inc.
• First Published: First published in Molecular and Cellular Proteomics 13(10):2705-2724
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher