A pathogen effector co-opts a host RabGAP protein to remodel pathogen interface and subvert defense-related secretion

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Yuen, Enoch Lok Him, Tumtas, Yasin, King, Freddie, Ibrahim, Tarhan, Chan, Lok I., Evangelisti, Edouard, Tulin, Frej, Skłenar, Jan, Menke, Frank L. H., Kamoun, Sophien, Bubeck, Doryen, Schornack, Sebastian and Bozkurt, Tolga Osman (2024) A pathogen effector co-opts a host RabGAP protein to remodel pathogen interface and subvert defense-related secretion. Science Advances, 10 (40). ISSN 2375-2548

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Abstract

Pathogens have evolved sophisticated mechanisms to manipulate host cell membrane dynamics, a crucial adaptation to survive in hostile environments shaped by innate immune responses. Plant-derived membrane interfaces, engulfing invasive hyphal projections of fungal and oomycete pathogens, are prominent junctures dictating infection outcomes. Understanding how pathogens transform these host-pathogen interfaces to their advantage remains a key biological question. Here, we identified a conserved effector, secreted by plant pathogenic oomycetes, that co-opts a host Rab GTPase-activating protein (RabGAP), TOPGAP, to remodel the host-pathogen interface. The effector, PiE354, hijacks TOPGAP as a susceptibility factor to usurp its GAP activity on Rab8a, a key Rab GTPase crucial for defense-related secretion. By hijacking TOPGAP, PiE354 purges Rab8a from the plasma membrane, diverting Rab8a-mediated immune trafficking away from the pathogen interface. This mechanism signifies an uncanny evolutionary adaptation of a pathogen effector in co-opting a host regulatory component to subvert defense-related secretion, thereby providing unprecedented mechanistic insights into the reprogramming of host membrane dynamics by pathogens.

Item Type:	Article
Additional Information:	Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. AF2-M predictions are uploaded to the public repository figshare and are available at https://doi.org/10.6084/m9.figshare.24846558. The constructs generated by the Schornack lab can be provided by S.S. pending a completed material transfer agreement. Requests for these materials should be submitted to sebastian.schornack@slcu.cam.ac.uk. Funding information: E.L.H.Y. is funded by BBSRC grants (BB/X511055/1) and (BB/X016382/1). Y.T. and T.O.B. are funded by BBSRC grant (BB/T006102/1). T.I. is funded by BBSRC grant (BB/X511055/1). E.E. and F.T. are funded by European Research Council (ERC-2014-STG, H2020, and 637537). S.S. is funded by Gatsby Foundation (GAT3395/GLD) and Royal Society (RG69135).
Faculty \ School:	Faculty of Science > The Sainsbury Laboratory Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Plant Sciences
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	24 Oct 2024 16:30
Last Modified:	06 Feb 2025 12:21
URI:	https://ueaeprints.uea.ac.uk/id/eprint/97187
DOI:	10.1126/sciadv.ado9516

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