What makes a man a man: Male development of Plasmodium falciparum

Voices in Infection Biology

  • Datum: 05.02.2025
  • Uhrzeit: 16:00
  • Vortragende(r): Gabriele Pradel
  • RWTH Aachen University
  • Ort: Max Planck Institute for Infection Biology
  • Raum: seminar room 1+2
  • Gastgeber: Silvia Portugal
  • Kontakt: vseminars@mpiib-berlin.mpg.de
What makes a man a man: Male development of <i>Plasmodium falciparum</i>

Abstract:

Across the animal kingdom, sex determination is regulated by a variety of factors. Not all animal groups have sex chromosomes, and while the majority of species possess a master-switch sex-determining gene, quantitative threshold traits of multiple gene products are also possible. In the protozoan malaria parasite Plasmodium falciparum, the master regulator AP2-G reprograms the asexual blood stages for sexual development leading to gametocytogenesis. Once synthesized, AP2-G activates downstream genes, like ones encoding the transcription factors AP2-FG and AP2-O3, which promote female gene profiles in the developing gametocytes, while repressing male genes. Various recent studies have unveiled a crucial role of zinc finger proteins (ZFPs) during the regulation of sex determination in gametocytes. These include the CCCH-ZFPs MD3 and ZNF4 as well as the RING finger E3 ligase RNF1. We show that parasites deficient of MD3 are impaired in gametocyte maturation and that lack of MD3 leads to a sex-ratio shift towards females. ZNF4 deficiency, on the other hand, impairs male gametogenesis by downregulation of male-enriched genes associated to axoneme formation. Further, MD3 and RNF1 share an interactome particularly involvingRNA-binding proteins crucial for sexual differentiation and gametogenesis like translational repressors as well as members of the recently identified group of regulators of sexual development, e.g. GD1 and FD2. In addition, we identified several yet unknown proteins specifically expressed in male or female gametocytes as interactors of MD3 and RNF1. We conclude that the three ZFPs are part of a regulator complex crucial for post-transcriptional fine-tuning of male gametocytogenesis.

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