title: Calcium-mediated protein secretion potentiates motility in Toxoplasma gondii.
abstract: Apicomplexans such as Toxoplasma gondii actively invade host cells using a unique parasite-dependent mechanism termed gliding motility. Calcium-mediated protein secretion by the parasite has been implicated in this process, but the precise role of calcium signaling in motility remains unclear. Here we used calmidazolium as a tool to stimulate intracellular calcium fluxes and found that this drug led to enhanced motility by T. gondii. Treatment with calmidazolium increased the duration of gliding and resulted in trails that were twice as long as those formed by control parasites. Calmidazolium also increased microneme secretion by T. gondii, and studies with a deletion mutant of the accessory protein m2AP specifically implicated that adhesin MIC2 was important for gliding. The effects of calmidazolium on gliding and secretion were due to increased release of calcium from intracellular stores and calcium influx from the extracellular milieu. In addition, we demonstrate that calmidazolium-stimulated increases in intracellular calcium were highly dynamic, and that rapid fluxes in calcium levels were associated with parasite motility. Our studies suggest that oscillations in intracellular calcium levels may regulate microneme secretion and control gliding motility in T. gondii.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Wetzel
authors.forename: Lea Ann
authors.initials: LA
authors.lastname: Chen
authors.forename: Felix A
authors.initials: FA
authors.lastname: Ruiz
authors.forename: Silvia N J
authors.initials: SN
authors.lastname: Moreno
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D017353:Gene Deletion; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009068:Movement; D009991:Oscillometry; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014122:Toxoplasma / Q000378:metabolism / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; C408878:MIC2 protein, Toxoplasma gondii; D008565:Membrane Proteins; D015800:Protozoan Proteins; C450759:TgM2AP protein, Toxoplasma gondii; C031938:calmidazolium; D001616:beta-Galactosidase; D002118:Calcium