title: Parasite Calcineurin Regulates Host Cell Recognition and Attachment by Apicomplexans.
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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Aditya S
authors.initials: AS
authors.lastname: Paul
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Saha
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Klemens
authors.initials: K
authors.lastname: Engelberg
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Rays H Y
authors.initials: RH
authors.lastname: Jiang
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Bradley I
authors.initials: BI
authors.lastname: Coleman
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Aziz L
authors.initials: AL
authors.lastname: Kosber
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Chun-Ti
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Ganter
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Espy
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; Centre for Structural Systems Biology, 22607 Hamburg, Germany.
authors.forename: Tim W
authors.initials: TW
authors.lastname: Gilberger
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Marc-Jan
authors.initials: MJ
authors.lastname: Gubbels
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: mduraisi@hsph.harvard.edu.
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
mesh_terms: D019703:Calcineurin / Q000378:metabolism*; D002448:Cell Adhesion; D004912:Erythrocytes / Q000469:parasitology; D005347:Fibroblasts / Q000469:parasitology; D006801:Humans; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000502:physiology*; D014122:Toxoplasma / Q000201:enzymology* / Q000502:physiology*
chemical_list: D019703:Calcineurin