Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex

Naito, Takashi; Ercan, Bilge; Krshnan, Logesvaran; Triebl, Alexander; Koh, Dylan Hong Zheng; Wei, Fan Yan; Tomizawa, Kazuhito; Torta, Federico; Wenk, Markus R.; Saheki, Yasunori

doi:10.7554/elife.51401

Cited by 133 publications

(193 citation statements)

References 103 publications

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“…Unglycosylated sterols and glycosylated sterols (including steryl glycosides and acyl sterol glycosides) are integral components of the plant plasma membranes, especially in membrane microdomains (50, 74). The increase in host acyl-glycosylated phytosterols by DSF treatment shown in our targeted lipidomic analysis might be a consequence of direct sterol modifications – such as DSF being metabolized to a precursor of acyl source for steryl glucoside acyltransferase (75), or from a potential sterol exchange between PM and ER through PM-ER contact sites (76, 77) — both of which require further investigation. Through the modulation of sterols, DSF interferes with plant PTI through the alteration of both the clustering and endocytic internalization of the surface receptors.…”

Section: Discussionmentioning

confidence: 99%

The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

Tran

Triebl

et al. 2020

Preprint

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36Quorum sensing (QS) is a recognized phenomenon that is crucial for regulating population-37 related behaviors in bacteria. However, the direct specific effect of QS molecules on host biology is 38 largely under-studied. In this work, we show that the QS molecule DSF (cis-11-methyl-dodecenoic acid) 39 produced by Xanthomonas campestris pv. campestris can suppress pathogen-associated molecular 40 pattern (PAMP)-triggered immunity (PTI) in Arabidopsis thaliana, mediated by flagellin-induced activation 41 of flagellin receptor FLS2. The DSF-mediated attenuation of innate immunity results from the alteration of 42 oligomerization states and endocytic internalization of plasma membrane FLS2. DSF altered the lipid 43 profile of Arabidopsis, with a particular increase of the phytosterol species, which impairs the general 44 endocytosis pathway mediated by clathrin and FLS2 nano-clustering on the plasma membrane. The DSF 45 effect on receptor dynamics and host immune responses could be entirely reversed by sterol removal. 46Together, our results highlighted the importance of sterol homeostasis to plasma membrane organization 47 and demonstrate a novel mechanism by which pathogenic bacteria use their communicating molecule to 48 manipulate PAMP-triggered host immunity. 49 50 Keywords: quorum sensing, plasma membrane, endocytosis, plant-pathogen interaction 51 52 SIGNIFICANCE STATEMENT 53Bacteria rely on small signalling molecules called quorum sensing (QS) signals to communicate 54 and coordinate their behaviors. QS is known to regulate gene expression, production of virulence factors, 55 and biofilm formation for pathogenic bacteria to effectively colonize their hosts and cause diseases. In this 56 work, we found a class of QS molecule called diffusible-signal factor (DSF), produced by devastating 57 phytopathogenic bacteria such as Xanthomonas spp. and Xylella fastidiosa, could communicate directly 58 with plant host and subvert plant innate immunity by inducing plant sterol production and thereby, 59 attenuating receptor signalling through hindering the receptor clustering and plant endocytosis. The 60 results significantly enrich our understanding of the mechanisms in the tug-of-war between bacterial 61 pathogenesis and host immunity. 62 63 infection (4). The 3OC12-HSL was also shown to be recognized by the bitter taste receptor, T2R family 73 protein, T2R38 in neutrophils, lymphocytes and monocytes to activate innate immune responses (5). 74Similarly, plant pathogenic bacteria also secrete small-molecule virulence factors to cross-talk with host 75 and manipulate host immunity during infection. QS molecules produced by several bacterial 76 phytopathogens showed a wide range of interference in host development and defence mechanisms, 77including the root morphological development in an auxin-dependent manner or callose deposition during 78 immune responses (6-8). However, the detailed mechanisms of how QS molecules directly influence 79 plant host development and pathology, especially the PAMP-mediated host immunity,...

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Section: Discussionmentioning

confidence: 99%

The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

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Triebl

et al. 2020

Preprint

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“…Their location in the very small spaces in contact sites may confer various advantages 68,71 . The active form of cholesterol is the substrate transported from the plasma membrane to the ER by the Aster/GRAMD1 complex 79,80 …”

Section: Intracellular Cholesterol Transportmentioning

confidence: 99%

Active cholesterol 20 years on

Lange

Steck

2020

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This review considers the following hypotheses, some well‐supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with bilayer phospholipids in complexes of varied strength and stoichiometry. These complexes underlie many of the material properties of the bilayer. The small fraction of cholesterol molecules exceeding the binding capacity of the phospholipids is thermodynamically active and serves diverse functions. It circulates briskly among the cell membranes, particularly through contact sites linking the organelles. Active cholesterol provides the upstream feedback signal to multiple mechanisms governing plasma membrane homeostasis, pegging the sterol level to a threshold set by its phospholipids. Active cholesterol could also be the cargo for various inter‐organelle transporters and the form excreted from cells by reverse transport. Furthermore, it is integral to the function of caveolae; a mediator of Hedgehog regulation; and a ligand for the binding of cytolytic toxins to membranes. Active cholesterol modulates a variety of plasma membrane proteins—receptors, channels and transporters—at least in vitro.

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“…The pathway between cholesterol removal from plasma membrane and its subsequent transport to the ER represents a field of extensive investigation aimed to identify specific transporters involved in the regulation of cholesterol homeostasis. Recent studies identified Aster/GRAMD1 as essential transporters of cholesterol into ER and regulating the cellular uptake of HDL-derived cholesterol ( Sandhu et al, 2018 ; Naito et al, 2019 ). ORP2 protein was also identified as a unique transporter of cholesterol from ER to the plasma membrane ( Wang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

New Insights Into Targeting Membrane Lipids for Cancer Therapy

Preta

2020

Front. Cell Dev. Biol.

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Modulation of membrane lipid composition and organization is currently developing as an effective therapeutic strategy against a wide range of diseases, including cancer. This field, known as membrane-lipid therapy, has risen from new discoveries on the complex organization of lipids and between lipids and proteins in the plasma membranes. Membrane microdomains present in the membrane of all eukaryotic cells, known as lipid rafts, have been recognized as an important concentrating platform for protein receptors involved in the regulation of intracellular signaling, apoptosis, redox balance and immune response. The difference in lipid composition between the cellular membranes of healthy cells and tumor cells allows for the development of novel therapies based on targeting membrane lipids in cancer cells to increase sensitivity to chemotherapeutic agents and consequently defeat multidrug resistance. In the current manuscript strategies based on influencing cholesterol/sphingolipids content will be presented together with innovative ones, more focused in changing biophysical properties of the membrane bilayer without affecting the composition of its constituents.

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Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex

Cited by 133 publications

References 103 publications

The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

The bacterial quorum sensing signal DSF hijacksArabidopsis thalianasterol biosynthesis to suppress plant innate immunity

Active cholesterol 20 years on

New Insights Into Targeting Membrane Lipids for Cancer Therapy

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