The transcriptional regulator HDP1 controls expansion of the inner membrane complex during early sexual differentiation of malaria parasites

Riward A. Campelo Morillo, Xinran Tong, Wei Xie, Steven Abel, Lindsey M. Orchard, Wassim Daher, Dinshaw J. Patel, Manuel Llinás, Karine G. Le Roch, Björn F.C. Kafsack

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Transmission of Plasmodium falciparum and other malaria parasites requires their differentiation from asexual blood stages into gametocytes, the non-replicative sexual stage necessary to infect the mosquito vector. This transition involves changes in gene expression and chromatin reorganization that result in the activation and silencing of stage-specific genes. However, the genomes of malaria parasites have been noted for their limited number of transcriptional and chromatin regulators, and the molecular mediators of these changes remain largely unknown. We recently identified homeodomain protein 1 (HDP1) as a DNA-binding protein, first expressed in gametocytes, that enhances the expression of key genes critical for early sexual differentiation. The discovery of HDP1 marks a new class of transcriptional regulator in malaria parasites outside of the better-characterized ApiAP2 family. Here, using molecular biology, biochemistry and microscopy techniques, we show that HDP1 is essential for gametocyte maturation, facilitating the necessary upregulation of inner membrane complex components during early gametocytogenesis that gives P. falciparum gametocytes their characteristic shape.

Original languageEnglish (US)
Pages (from-to)289-299
Number of pages11
JournalNature Microbiology
Volume7
Issue number2
DOIs
StatePublished - Feb 2022

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

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