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Cell Host Microbe. 2015 Jul 8;18(1):49-60. doi: 10.1016/j.chom.2015.06.003. Epub 2015 Jun 25.

Parasite Calcineurin Regulates Host Cell Recognition and Attachment by Apicomplexans.

Author information

1
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
2
Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
3
Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; Centre for Structural Systems Biology, 22607 Hamburg, Germany.
4
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: mduraisi@hsph.harvard.edu.

Abstract

Apicomplexans invade a variety of metazoan host cells through mechanisms involving host cell receptor engagement and secretion of parasite factors to facilitate cellular attachment. We find that the parasite homolog of calcineurin, a calcium-regulated phosphatase complex central to signal transduction in eukaryotes, also contributes to host cell invasion by the malaria parasite Plasmodium falciparum and related Toxoplasma gondii. Using reverse-genetic and chemical-genetic approaches, we determine that calcineurin critically regulates and stabilizes attachment of extracellular P. falciparum to host erythrocytes before intracellular entry and has similar functions in host cell engagement by T. gondii. Calcineurin-mediated Plasmodium invasion is strongly associated with host receptors required for host cell recognition, and calcineurin function distinguishes this form of receptor-mediated attachment from a second mode of host-parasite adhesion independent of host receptors. This specific role of calcineurin in coordinating physical interactions with host cells highlights an ancestral mechanism for parasitism used by apicomplexans.

PMID:
26118996
PMCID:
PMC4506782
DOI:
10.1016/j.chom.2015.06.003
[Indexed for MEDLINE]
Free PMC Article

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