Genetic crosses and complementation reveal essential functions for the Plasmodium stage-specific actin2 in sporogonic development

Cell Microbiol. 2014 May;16(5):751-67. doi: 10.1111/cmi.12274. Epub 2014 Feb 20.

Abstract

Malaria parasites have two actin isoforms, ubiquitous actin1 and specialized actin2. Actin2 is essential for late male gametogenesis, prior to egress from the host erythrocyte. Here, we examined whether the two actins fulfil overlapping functions in Plasmodium berghei. Replacement of actin2 with actin1 resulted in partial complementation of the defects in male gametogenesis and, thus, viable ookinetes were formed, able to invade the midgut epithelium and develop into oocysts. However, these remained small and their DNA was undetectable at day 8 after infection. As a consequence sporogony did not occur, resulting in a complete block of parasite transmission. Furthermore, we show that expression of actin2 is tightly controlled in female stages. The actin2 transcript is translationally repressed in female gametocytes, but translated in female gametes. The protein persists until mature ookinetes; this expression is strictly dependent on the maternally derived expression. Genetic crosses revealed that actin2 functions at an early stage of ookinete formation and that parasites lacking actin2 are unable to undergo sporogony in the mosquito midgut. Our results provide insights into the specialized role of actin2 in Plasmodium development in the mosquito and suggest that the two actin isoforms have distinct biological functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Crosses, Genetic
  • Culicidae / parasitology
  • Genetic Complementation Test
  • Intestinal Mucosa / parasitology
  • Plasmodium berghei / cytology
  • Plasmodium berghei / genetics*
  • Plasmodium berghei / growth & development*
  • Spores, Protozoan / cytology
  • Spores, Protozoan / genetics*
  • Spores, Protozoan / growth & development*

Substances

  • Actins