TY - JOUR
T1 - A pathogen effector co-opts a host RabGAP protein to remodel pathogen interface and subvert defense-related secretion
AU - Yuen, Enoch Lok Him
AU - Tumtas, Yasin
AU - King, Freddie
AU - Ibrahim, Tarhan
AU - Chan, Lok I.
AU - Evangelisti, Edouard
AU - Tulin, Frej
AU - Skłenar, Jan
AU - Menke, Frank L. H.
AU - Kamoun, Sophien
AU - Bubeck, Doryen
AU - Schornack, Sebastian
AU - Bozkurt, Tolga Osman
N1 - 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 [email protected].
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).
PY - 2024/10/4
Y1 - 2024/10/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85205828738&partnerID=8YFLogxK
U2 - 10.1126/sciadv.ado9516
DO - 10.1126/sciadv.ado9516
M3 - Article
C2 - 39365859
AN - SCOPUS:85205828738
SN - 2375-2548
VL - 10
JO - Science Advances
JF - Science Advances
IS - 40
M1 - eado9516
ER -