External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectors into Plant and Animal Host Cells

Kale, Shiv D.; Gu, Biao; Capelluto, Daniel G. S.; Dou, Daolong; Feldman, Emily R.; Rumore, Amanda; Arredondo, Francisco; Hanlon, Regina; Fudal, Isabelle; Rouxel, Thierry; Lawrence, Christopher B.; Shan, Weixing; Tyler, Brett M.

doi:10.1016/j.cell.2010.06.008

Cited by 415 publications

(304 citation statements)

References 47 publications

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“…In addition to these, the fungal defensin plectasin from Pseudoplectania nigrella, which shares the same plant defensin CS␣␤ architecture, exhibits growth-inhibitory activity against Gram-positive bacteria through direct binding to the cell wall precursor lipid II (40). It has also been reported that the effector protein from the fungus-like oomycete pathogen binds to outer membrane PI(3)P through a conserved cationic motif to enable entry into host cells (41). Taken together, these observations support the hypothesis that the lipid-binding fungal and plant defensins target a wide range of lipids across different species and that this lipid-targeting mechanism extends back into the early evolution of eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

The Tomato Defensin TPP3 Binds Phosphatidylinositol (4,5)-Bisphosphate via a Conserved Dimeric Cationic Grip Conformation To Mediate Cell Lysis

Baxter

Richter

Lay

et al. 2015

Molecular and Cellular Biology

104

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Defensins are a class of ubiquitously expressed cationic antimicrobial peptides (CAPs) that play an important role in innate defense. Plant defensins are active against a broad range of microbial pathogens and act via multiple mechanisms, including cell membrane permeabilization. The cytolytic activity of defensins has been proposed to involve interaction with specific lipid components in the target cell wall or membrane and defensin oligomerization. Indeed, the defensin Nicotiana alata defensin 1 (NaD1) binds to a broad range of membrane phosphatidylinositol phosphates and forms an oligomeric complex with phosphatidylinositol (4,5)-bisphosphate (PIP2) that facilitates membrane lysis of both mammalian tumor and fungal cells. Here, we report that the tomato defensin TPP3 has a unique lipid binding profile that is specific for PIP2 with which it forms an oligomeric complex that is critical for cytolytic activity. Structural characterization of TPP3 by X-ray crystallography and site-directed mutagenesis demonstrated that it forms a dimer in a "cationic grip" conformation that specifically accommodates the head group of PIP2 to mediate cooperative higher-order oligomerization and subsequent membrane permeabilization. These findings suggest that certain plant defensins are innate immune receptors for phospholipids and adopt conserved dimeric configurations to mediate PIP2 binding and membrane permeabilization. This mechanism of innate defense may be conserved across defensins from different species. P lant defensins are small (ϳ5 kDa), cysteine-rich, cationic peptides that belong to the broad class of innate defense molecules known as cationic antimicrobial peptides (CAPs). Plant defensins play a major role in plant innate immunity and have been identified in all analyzed plant species to date, as either constitutively expressed or induced defense molecules that are produced in response to pathogenic attack or environmental stress (1). The tertiary structure of all plant defensins is highly conserved, comprising a triple-stranded antiparallel ␤-sheet and a single ␣-helix stabilized by four disulfide bridges, known as the "cysteine-stabilized alpha-beta" or "CS␣␤" motif (2). Despite this conserved three-dimensional structure, there is a high degree of variation in the primary sequence of plant defensins, particularly at intervening loop regions, which are typically important for activity (3).Many plant defensins have antifungal activity, but other functions have been reported, including antibacterial activity, ion channel blocking, protein synthesis inhibition, and trypsin and ␣-amylase inhibition as well as roles in heavy metal tolerance, plant development, and pollen tube guidance (3-5). They can be divided into two classes based on whether or not a C-terminal propeptide (CTPP) (of ϳ33 amino acids) is present (2, 6). This domain is involved in vacuolar targeting and protects the plant cells from phytotoxicity during transit through the secretory pathway (7). Defensins expressed with the additional CTPP domain are kn...

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Section: Discussionmentioning

confidence: 99%

The Tomato Defensin TPP3 Binds Phosphatidylinositol (4,5)-Bisphosphate via a Conserved Dimeric Cationic Grip Conformation To Mediate Cell Lysis

Baxter

Richter

Lay

et al. 2015

Molecular and Cellular Biology

104

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“…Once expressed, this effector passes through the plant secretory system and is secreted into the extracellular space (apoplast); its subsequent reentry into the plant cell can then be traced microscopically via fusion to a fluorescent protein (70). Through the generation of mutations in specific domains suspected to function in delivery of effectors into plant cells and by employing cell reentry assays, it has been possible to identify putative domains required for entry (65,71,72). However, this assay cannot unequivocally demonstrate that when the effector is expressed, it is assuredly secreted into the apoplast prior to reentry.…”

Section: How Are Effectors Deployed In the Host?mentioning

confidence: 99%

Oomycete Interactions with Plants: Infection Strategies and Resistance Principles

Fawke

Doumane

Schornack

2015

Microbiol Mol Biol Rev

176

159

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SUMMARY The Oomycota include many economically significant microbial pathogens of crop species. Understanding the mechanisms by which oomycetes infect plants and identifying methods to provide durable resistance are major research goals. Over the last few years, many elicitors that trigger plant immunity have been identified, as well as host genes that mediate susceptibility to oomycete pathogens. The mechanisms behind these processes have subsequently been investigated and many new discoveries made, marking a period of exciting research in the oomycete pathology field. This review provides an introduction to our current knowledge of the pathogenic mechanisms used by oomycetes, including elicitors and effectors, plus an overview of the major principles of host resistance: the established R gene hypothesis and the more recently defined susceptibility (S) gene model. Future directions for development of oomycete-resistant plants are discussed, along with ways that recent discoveries in the field of oomycete-plant interactions are generating novel means of studying how pathogen and symbiont colonizations overlap.

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“…To examine whether Ras isoforms differentially sort membrane lipids, we used lipid-binding or PH probes to spatially map the distributions of PS (GFP-LactC2) (27,31), phosphatidic acid (PA) (GFP-PH-Spo20) (33), phosphatidylinositol 4,5-bisphosphate (PIP 2 ) (GFP-PH-PLC␦) (34), phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) (GFP-PHAkt) (35), phosphatidylinositol 3-phosphate (PI 3 P) (GFP-PH-FYVE) (36), and phosphatidylinositol 4-phosphate (PI 4 P) (GFP-FAPP1) (37) with respect to Ras nanoclusters on intact PMs (Fig. 1a).…”

Section: Ras Nanoclusters Have Different Lipid Compositions But Allmentioning

confidence: 99%

Signal Integration by Lipid-Mediated Spatial Cross Talk between Ras Nanoclusters

Zhou

Luan

Rodkey

et al. 2014

Molecular and Cellular Biology

128

245

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b Lipid-anchored Ras GTPases form transient, spatially segregated nanoclusters on the plasma membrane that are essential for high-fidelity signal transmission. The lipid composition of Ras nanoclusters, however, has not previously been investigated. High-resolution spatial mapping shows that different Ras nanoclusters have distinct lipid compositions, indicating that Ras proteins engage in isoform-selective lipid sorting and accounting for different signal outputs from different Ras isoforms. Phosphatidylserine is a common constituent of all Ras nanoclusters but is only an obligate structural component of K-Ras nanoclusters. Segregation of K-Ras and H-Ras into spatially and compositionally distinct lipid assemblies is exquisitely sensitive to plasma membrane phosphatidylserine levels. Phosphatidylserine spatial organization is also modified by Ras nanocluster formation. In consequence, Ras nanoclusters engage in remote lipid-mediated communication, whereby activated H-Ras disrupts the assembly and operation of spatially segregated K-Ras nanoclusters. Computational modeling and experimentation reveal that complex effects of caveolin and cortical actin on Ras nanoclustering are similarly mediated through regulation of phosphatidylserine spatiotemporal dynamics. We conclude that phosphatidylserine maintains the lateral segregation of diverse lipid-based assemblies on the plasma membrane and that lateral connectivity between spatially remote lipid assemblies offers important previously unexplored opportunities for signal integration and signal processing. H-, N-, and K-Ras are small GTPases that operate as molecular switches to regulate cell growth, proliferation, and differentiation (1, 2). H-, N-, and K-Ras comprise nearly identical G domains (amino acids 1 to 165), which bind guanine nucleotides and interact with effectors and exchange factors, but they contain highly divergent C-terminal hypervariable regions (HVRs) (3, 4). The HVR undergoes posttranslational processing to attach a membrane anchor, which consists of a C-terminal S-farnesyl cysteine carboxylmethyl ester (common to all Ras proteins) and mono-palmitoylation of N-Ras, di-palmitoylation of H-Ras, and the presence of a polylysine domain in K-Ras (5-8). Ras proteins are distributed heterogeneously over the plasma membrane (PM) in a combination of immobile nanoclusters and freely diffusing monomers (9). A nanocluster comprises ϳ7 Ras proteins, has a radius of ϳ9 nm, and has an estimated lifetime of 0.5 to 1 s (10, 11). Nanocluster formation is essential for high-fidelity signal transmission (11-16). As a direct consequence of the different lipid anchors and different residues in the flanking HVR and G domain, which directly participate in membrane binding, N-, H-, and K-Ras assemble into spatially nonoverlapping nanoclusters, with further lateral segregation into nonoverlapping GDP and GTP nanoclusters (11,(16)(17)(18)(19)(20)(21)(22)(23).Ras isoforms exhibit different effector activation profiles (1). To account for isoform-specific signal output, Ras ...

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External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectors into Plant and Animal Host Cells

Cited by 415 publications

References 47 publications

The Tomato Defensin TPP3 Binds Phosphatidylinositol (4,5)-Bisphosphate via a Conserved Dimeric Cationic Grip Conformation To Mediate Cell Lysis

The Tomato Defensin TPP3 Binds Phosphatidylinositol (4,5)-Bisphosphate via a Conserved Dimeric Cationic Grip Conformation To Mediate Cell Lysis

Oomycete Interactions with Plants: Infection Strategies and Resistance Principles

Signal Integration by Lipid-Mediated Spatial Cross Talk between Ras Nanoclusters

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