C-terminal processing of the toxoplasma protein MIC2 is essential for invasion into host cells.
Host cell invasion by apicomplexan parasites is accompanied by the rapid, polarized secretion of parasite proteins that are involved in cell attachment. The Toxoplasma gondii micronemal protein MIC2 contains several extracellular adhesive domains, a transmembrane domain, and a short cytoplasmic tail. Following apical secretion, MIC2 is transiently present on the parasite surface before being translocated backward and released by proteolytic cleavage. Mutations in the extracellular domain of MIC2, directly upstream of the transmembrane domain, prevented processing and release of the soluble protein into the supernatant. A conserved basic residue in MIC2 was essential for cleavage, and basic residues are similarly positioned in other microneme proteins. Following the induction of secretion, MIC2 processing mutants were stably expressed on the surface of the parasite. Surface MIC2-expressing mutants showed increased adhesion to host cells, yet were impaired in their capacity to invade. These data demonstrate that proteolysis is essential for releasing cell surface adhesins prior to cell entry by apicomplexan parasites.
Brossier
Fabien
F
Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Jewett
Travis J
TJ
Lovett
Jennie L
JL
Sibley
L David
LD
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000469:parasitology; D002478:Cells, Cultured; D000939:Epitopes / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology / Q000469:parasitology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000166:cytology / Q000469:parasitology; D014122:Toxoplasma / Q000472:pathogenicity* / Q000502:physiology
D000939:Epitopes; C408878:MIC2 protein, Toxoplasma gondii; D008565:Membrane Proteins; D015800:Protozoan Proteins