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A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium
Abhinav Sinha1, Katie R Hughes1, Katarzyna K Modrzynska2
1Wellcome Trust Centre for Molecular Parasitology, University of Glasgow.
Nature
|February 28, 2014
Summary
A key protein, PbAP2-G, drives sexual development commitment in malaria parasites, enabling mosquito transmission. This discovery reveals a molecular mechanism that could be targeted to block malaria transmission.
Area of Science:
- Molecular biology
- Parasitology
- Genetics
Background:
- Sexual development in Plasmodium parasites is crucial for transmission to mosquitoes.
- The molecular mechanisms regulating this commitment have remained largely unknown.
- Understanding these mechanisms is vital for developing transmission-blocking strategies.
Purpose of the Study:
- To identify the molecular factors responsible for commitment to sexual development in Plasmodium.
- To elucidate the role of apicomplexan AP2 (ApiAP2) transcription factors in this process.
- To explore potential targets for interrupting malaria parasite transmission.
Main Methods:
- Gene deletion and mutation analysis in Plasmodium berghei.
- Identification and characterization of ApiAP2 family members.
- Investigation of gene function in parasite sexual development.
Main Results:
- PbAP2-G, an ApiAP2 DNA-binding protein, is essential for commitment to sexual development in P. berghei.
- Mutations in PbAP2-G lead to a loss of sexual development.
- A second ApiAP2 protein, PbAP2-G2, modulates gametocytogenesis, suggesting a cascade mechanism.
- A positive feedback loop involving PbAP2-G in gametocytogenesis is proposed.
Conclusions:
- PbAP2-G plays a critical role in the commitment to sexual development in malaria parasites.
- A cascade of ApiAP2 proteins regulates gametocytogenesis.
- The identified mechanism offers a potential target for preventing malaria transmission.
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