Traffic control: Functional principles of RabGAPs in plant immunity and vesicle trafficking
File(s)
Author(s)
Yuen, Lok Him
Type
Thesis
Abstract
Pathogens adeptly manipulate the dynamics of host cell membranes, a crucial survival adaptation in hostile environments shaped by the host immune system. At the heart of this manipulation are host-pathogen interfaces, where plant-derived membranes encase invasive hyphal projections of fungal and oomycete pathogens. Here, plants strategically reorient their defences, exerting a focal influence on infection outcomes. The exploration of how pathogens exploit these interfaces remains a fundamental biological question. This research uncovers a conserved effector, PiE354, secreted by the plant pathogenic oomycetes Phytophthora, which co-opts the host Rab GTPase-activating protein (RabGAP), TBC1D15L, to reshape the host-pathogen interface. PiE354 strategically targets TBC1D15L as a susceptibility factor, manipulating its GAP activity on Rab8a, a pivotal Rab GTPase crucial for defence-related secretion. Through this interaction, PiE354 redirects Rab8a-mediated immune trafficking away from the pathogen interface and towards the vacuole. Notably, TBC1D15L is guarded against effector manipulation by nucleotide-binding, leucine-rich-repeat receptors (NLRs) in N. benthamiana. Intriguingly, PiE354 not only evades immune recognition, but also suppresses the defence responses triggered by its homologues E19 and PiE355. Additionally, I unravelled an intramolecular regulatory mechanism within TBC1D15L which controls the essential GAP function that is guarded by NLRs against effector manipulation. This research extends beyond plant immunity, as I uncovered that TBC1D15L also regulates autophagy by binding to the host autophagy protein ATG8CL. Thus, this work positions TBC1D15L at the regulatory crossroad of plant immunity and autophagy. Altogether, this effector targeting mechanism underscores an intriguing evolutionary adaptation, wherein PiE354 co-opts a host regulatory component to subvert defence-related secretion. The PiE354-TBC1D15L-Rab8a interaction system serves as a distinctive model for delving into how effectors manipulate host cell trafficking systems and thwart effector-triggered immunity (ETI).
Version
Open Access
Date Issued
2024-01-06
Date Awarded
2024-06-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Bozkurt, Tolga
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)