期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.85171
关键词
toxoplasma; apicomplexa; traction force mapping; cell motility; Other
类别
资金
- National Institute of Allergy and Infectious Diseases [AI139201, AI137767]
- National Institute of General Medical Sciences [GM141743, S10OD026884]
- National Institute of Allergy and Infectious Diseases [T32AI055402, F31AI145214]
- American Heart Association [19PRE34370071]
Toxoplasma gondii is a protozoan parasite that infects a significant portion of the world's population, using a unique form of substrate-dependent motility to invade host cells and disseminate throughout the body. Recent research shows that the predominant forces exerted by the moving parasite are periodic and directed inward, leading to a visible constriction in the parasite's plasma membrane. This suggests a closer connection between parasite motility and host cell invasion than previously recognized.
Toxoplasma gondii is a protozoan parasite that infects 30-40% of the world's population. Infections are typically subclinical but can be severe and, in some cases, life threatening. Central to the virulence of T. gondii is an unusual form of substrate-dependent motility that enables the parasite to invade cells of its host and to disseminate throughout the body. A hetero-oligomeric complex of proteins that functions in motility has been characterized, but how these proteins work together to drive forward motion of the parasite remains controversial. A key piece of information needed to understand the underlying mechanism(s) is the directionality of the forces that a moving parasite exerts on the external environment. The linear motor model of motility, which has dominated the field for the past two decades, predicts continuous anterior-to-posterior force generation along the length of the parasite. We show here using three-dimensional traction force mapping that the predominant forces exerted by a moving parasite are instead periodic and directed in toward the parasite at a fixed circular location within the extracellular matrix. These highly localized forces, which are generated by the parasite pulling on the matrix, create a visible constriction in the parasite's plasma membrane. We propose that the ring of inward-directed force corresponds to a circumferential attachment zone between the parasite and the matrix, through which the parasite propels itself to move forward. The combined data suggest a closer connection between the mechanisms underlying parasite motility and host cell invasion than previously recognized. In parasites lacking the major surface adhesin, TgMIC2, neither the inward-directed forces nor the constriction of the parasite membrane are observed. The trajectories of the TgMIC2-deficient parasites are less straight than those of wild-type parasites, suggesting that the annular zone of TgMIC2-mediated attachment to the extracellular matrix normally constrains the directional options available to the parasite as it migrates through its surrounding environment.
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