Hueschen, Christina L. and Segev Zarko, Li-av and Chen, Jian-Hua and LeGros, Mark A. and Larabell, Carolyn A. and Boothroyd, John C. and Phillips, Rob and Dunn, Alexander R. (2022) Emergent Actin Flows Explain Diverse Parasite Gliding Modes. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20220614-222259000
Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20220614-222259000
Abstract
During host infection, single–celled apicomplexan parasites like Plasmodium and Toxoplasma use a motility mechanism called gliding, which differs fundamentally from other known mechanisms of eukaryotic cell motility. Gliding is thought to be powered by a thin layer of flowing filamentous (F)–actin sandwiched between the plasma membrane and a myosin–coated inner membrane complex. How this surface actin layer drives the diverse apicomplexan gliding modes observed experimentally – helical, circular, and twirling, and patch, pendulum, or rolling – presents a rich biophysical puzzle. Here, we use single–molecule imaging to track individual actin filaments and myosin complexes in live Toxoplasma gondii. Based on these data, we hypothesize that F–actin flows arise by self–organization, rather than following a microtubule-based template as previously believed. We develop a continuum model of emergent F–actin flow within the unusual confines provided by parasite geometry. In the presence of F–actin turnover, our model predicts the emergence of a steady–state mode in which actin transport is largely rearward. Removing actin turnover leads to actin patches that recirculate up and down the cell, a ″cyclosis″ that we observe experimentally for drug–stabilized actin bundles in live parasites. These findings provide a mechanism by which actin turnover governs a transition between distinct self–organized F–actin states, whose properties can account for the diverse gliding modes known to occur. More broadly, we illustrate how different forms of gliding motility can emerge as an intrinsic consequence of the self–organizing properties of F–actin flow in a confined geometry.
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Additional Information: | The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We are grateful for helpful discussions with colleagues and friends. We thank in particular Melanie Espiritu, Greg Huber, Elgin Korkmazhan, Madhav Mani, Mike Panas, Manu Prakash, Carlos Rojo, Suraj Shankar, Sho Takatori, Yuhai Tu, Vipul Vaccharajani, the Stanford Apicomplexa Supergroup, and members of the Dunn lab. Gary Ward, Rachel Stadler, and Deepak Krishnamurthy were invaluable sources of inspiration and guidance throughout. This work was supported by a Damon Runyon Fellowship Award (C.L.H.), a Burroughs Wellcome Career Award at the Scientific Interface (C.L.H.), NIH R35GM130332 (A.R.D.), an HHMI Faculty Scholar Award (A.R.D.), NIH MIRA 1R35 GM118043 (R.P.), and the Chan Zuckerberg Biohub Intercampus Team Award (J.C.B., C.A.L.). The soft X-ray tomography was conducted at the National Center for X-ray Tomography, which is supported by NIH NIGMS (P30GM138441) and the DOE’s Office of Biological and Environmental Research (DE-AC02-5CH11231). The Center is located at the Advanced Light Source, a U.S. DOE Office of Science User Facility under contract no. DE-AC02-05CH11231. Author Contributions. C.L.H., A.R.D., R.P., L.S.Z., and J.C.B. conceptualized the study; C.L.H., L.S.Z., and J.H.C. performed experiments; C.L.H. analyzed data with insight from A.R.D., R.P., and J.C.B.; C.L.H. and R.P. developed the theoretical model and performed computational studies; C.L.H., A.R.D., R.P., J.C.B., and C.A.L. provided funding; C.L.H., L.S.Z., A.R.D., R.P., J.H.C., M.A.L., C.A.L. and J.C.B. contributed to methodology; C.L.H. wrote the manuscript; C.L.H., A.R.D., R.P., L.S.Z., and J.C.B. reviewed and edited the manuscript. Data and materials availability: Data, MATLAB code, plasmids, and Toxoplasma gondii strains are available upon request. Code will be made available on Github by time of publication, and the link will be inserted here on bioRxiv. The authors have declared no competing interest. | ||||||||||||||||
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DOI: | 10.1101/2022.06.08.495399 | ||||||||||||||||
Record Number: | CaltechAUTHORS:20220614-222259000 | ||||||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20220614-222259000 | ||||||||||||||||
Official Citation: | Emergent Actin Flows Explain Diverse Parasite Gliding Modes Christina L. Hueschen, Li-av Segev Zarko, Jian-Hua Chen, Mark A. LeGros, Carolyn A. Larabell, John C. Boothroyd, Rob Phillips, Alexander R. Dunn bioRxiv 2022.06.08.495399; doi: https://doi.org/10.1101/2022.06.08.495399 | ||||||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||
ID Code: | 115152 | ||||||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||||||
Deposited By: | George Porter | ||||||||||||||||
Deposited On: | 15 Jun 2022 16:40 | ||||||||||||||||
Last Modified: | 15 Jun 2022 16:40 |
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