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Emergent Actin Flows Explain Diverse Parasite Gliding Modes

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 (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20220614-222259000

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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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2022.06.08.495399DOIDiscussion Paper
https://www.biorxiv.org/content/10.1101/2022.06.08.495399v1.supplementary-materialPublisherSupporting Information
ORCID:
AuthorORCID
Hueschen, Christina L.0000-0002-3437-2895
Segev Zarko, Li-av0000-0003-4151-5513
Chen, Jian-Hua0000-0002-7998-0878
Larabell, Carolyn A.0000-0002-6262-4789
Boothroyd, John C.0000-0001-9719-745X
Phillips, Rob0000-0003-3082-2809
Dunn, Alexander R.0000-0001-6096-4600
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.
Funders:
Funding AgencyGrant Number
Damon Runyon Cancer Research FoundationUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
NIHR35GM130332
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Chan-Zuckerberg BiohubUNSPECIFIED
NIHP30GM138441
Department of Energy (DOE)DE-AC02-5CH11231
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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