Conditional Degradation of Plasmodium Calcineurin Reveals Functions in Parasite Colonization of both Host and Vector

Cell Host Microbe. 2015 Jul 8;18(1):122-31. doi: 10.1016/j.chom.2015.05.018. Epub 2015 Jun 25.


Functional analysis of essential genes in the malarial parasite, Plasmodium, is hindered by lack of efficient strategies for conditional protein regulation. We report the development of a rapid, specific, and inducible chemical-genetic tool in the rodent malaria parasite, P. berghei, in which endogenous proteins engineered to contain the auxin-inducible degron (AID) are selectively degraded upon adding auxin. Application of AID to the calcium-regulated protein phosphatase, calcineurin, revealed functions in host and vector stages of parasite development. Whereas depletion of calcineurin in late-stage schizonts demonstrated its critical role in erythrocyte attachment and invasion in vivo, stage-specific depletion uncovered roles in gamete development, fertilization, and ookinete-to-oocyst and sporozoite-to-liver stage transitions. Furthermore, AID technology facilitated concurrent generation and phenotyping of transgenic lines, allowing multiple lines to be assessed simultaneously with significant reductions in animal use. This study highlights the broad applicability of AID for functional analysis of proteins across the Plasmodium life cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Calcineurin / genetics
  • Calcineurin / metabolism*
  • Culicidae
  • Host-Parasite Interactions*
  • Indoleacetic Acids / metabolism*
  • Mice
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / physiology*
  • Proteolysis / drug effects*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*


  • Indoleacetic Acids
  • Protozoan Proteins
  • Calcineurin