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Purpose of Review: To provide an update on the diagnosis of non-specific Lipid Transfer Protein (nsLTP) allergy., Recent Findings: More publications report the presence of nsLTP allergy in Northern European countries and nsLTP sensitisation in children. Individuals are more likely to have severe reactions if there is recognition of increasing numbers of LTP components. Diagnosis is problematic; not all those with nsLTP allergy will have a positive test to a peach extract containing Pru p 3, the peach nsLTP. Sensitisation to nsLTP is being reported in more countries, including to the nsLTP in Cannabis Sativa in North America. Meals containing multiple nsLTP foods are more likely to be involved in co-factor reactions. Component-resolved diagnostics are superior to skin prick tests, to determine sensitisation to the individual nsLTP allergens causing symptoms and, in the future, the Basophil Activation test may best discriminate between sensitization and clinical allergy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The adaption of plants to stressful environments depends on long-distance responses in plant organs, which themselves are remote from sites of perception of external stimuli. Jasmonic acid (JA) and its derivatives are known to be involved in plants' adaptation to salinity. However, to our knowledge, the transport of JAs from roots to shoots has not been studied in relation to the responses of shoots to root salt treatment. We detected a salt-induced increase in the content of JAs in the roots, xylem sap, and leaves of pea plants related to changes in transpiration. Similarities between the localization of JA and lipid transfer proteins (LTPs) around vascular tissues were detected with immunohistochemistry, while immunoblotting revealed the presence of LTPs in the xylem sap of pea plants and its increase with salinity. Furthermore, we compared the effects of exogenous MeJA and salt treatment on the accumulation of JAs in leaves and their impact on transpiration. Our results indicate that salt-induced changes in JA concentrations in roots and xylem sap are the source of accumulation of these hormones in leaves leading to associated changes in transpiration. Furthermore, they suggest the possible involvement of LTPs in the loading/unloading of JAs into/from the xylem and its xylem transport.

Lipid transfer proteins mediate nonvesicular transport of lipids at membrane contact sites to regulate the lipid composition of organelle membranes. Recently, a new type of bridge-like lipid transfer protein has emerged; these proteins contain a long hydrophobic groove and can mediate bulk transport of lipids between organelles. Here, we review recent insights into the structure of these proteins and identify a repeating modular unit that we propose to name the repeating β-groove (RBG) domain. This new structural understanding conceptually unifies all the RBG domain-containing lipid transfer proteins as members of an RBG protein superfamily. We also examine the biological functions of these lipid transporters in normal physiology and disease and speculate on the evolutionary origins of RBG proteins in bacteria., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Plant AMPs are usually cysteine-rich, and can be classified in several classes, including lipid transfer proteins (LTPs). LTPs are small plant cationic peptides, and can be classified in two subclasses, LTP 1 (9-10 kDa) and LTP 2 (7 kDa). They have been identified and isolated from various plant species and can be involved in a number of processes, including responses against several phytopathogens. LTP 1 presents 4 parallel α- helices and a 3 10 -helix fragment. These structures form a tunnel with large and small entrances. LTP 2 presents 3 parallel α- helices, which form a cavity with triangular structure. Both LTP subclasses present a hydrophobic cavity, which makes interaction with different lipids and general hydrophobic molecules possible. Several studies report a broad spectrum of activity of plant LTPs, including antibacterial, antifungal, antiviral, antitumoral, and insecticidal activity. Thus, these molecules can be employed in human and animal health as an alternative to the conventional treatment of disease, well as providing the source of novel drugs. However, employing peptides in human health can present challenges, such as the toxicity of peptides, the difference between the results found in in vitro assays and in pre-clinical or clinical tests and their low efficiency against Gram-negative bacteria. In this context, plant LTPs can be an interesting alternative means by which to bypass such challenges. This review addresses the versatility of plant LTPs, their broad spectrum of activities and their potential applications in human and animal health and in agricultural production, and examines challenges in their biotechnological application., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Component-resolved diagnosis reveals the IgE response to many inhaled, food, and other allergens, improving the understanding and diagnosis of allergic diseases., Objective: The aims of the study are to study the recognition of different lipid transfer proteins (LTPs) and other allergen families in a large group of people sensitized to Pru p 3 and to analyze the relationship between the clinical entities and the allergens., Methods: This cross-sectional study included a large cohort of patients with positive skin tests to peach fruit and Pru p 3 specific IgE antibodies. Respiratory and food allergy symptoms were collected, and we performed prick tests with pollen, plant food, and other allergens plus the ImmunoCAP ISAC assay., Results: Our sample consisted of 421 people with a mean age of 33.25 years (range 16-68); 54.6% were women. Clinical entities included anaphylaxis (37.1%), urticaria (67.9%), and oral allergy syndrome (59.1%). Rhinitis, rhinoconjunctivitis, and/or asthma were diagnosed in 71.8% of the participants. The most pronounced correlation existed between sensitization to Pru p 3 and to Jug r 3, Pla a 3, Ara h 9, and Cor a 8. We found a higher incidence of anaphylaxis in people with 5 or more recognized LTPs. No association was observed between inhaled and food allergies., Conclusion: Most Pru p 3-sensitized participants were sensitized to additional allergens from the same family and, to a lesser extent, to other allergens, mainly in the profilin and PR-10 protein families. Anaphylaxis occurred in more than a third of the cases evaluated, and almost three-quarters of them had respiratory symptoms. Respiratory and food allergies involving LTPs do not seem to be associated., (© 2020 S. Karger AG, Basel.)

Lipid transfer proteins (LTPs) are a class of small, cationic proteins that bind and transfer lipids and play an important role in plant defense. However, their precise biological role in plants under adverse conditions including salinity and possible regulation by stress hormone abscisic acid (ABA) remains unknown. In this work, we studied the localization of LTPs and ABA in the roots of pea plants using specific antibodies. Presence of LTPs was detected on the periphery of the cells mainly located in the phloem. Mild salt stress (50 mM NaCI) led to slowing plant growth and higher immunostaining for LTPs in the phloem. The deposition of suberin in Casparian bands located in the endoderma revealed with Sudan III was shown to be more intensive under salt stress and coincided with the increased LTP staining. All obtained data suggest possible functions of LTPs in pea roots. We assume that these proteins can participate in stress-induced pea root suberization or in transport of phloem lipid molecules. Salt stress increased ABA immunostaining in pea root cells but its localization was different from that of the LTPs. Thus, we failed to confirm the hypothesis regarding the direct influence of ABA on the level of LTPs in the salt-stressed root cells., Competing Interests: The authors declare no conflicts of interest.

The understanding of the role of sphingolipid metabolism in cancer has tremendously increased in the past ten years. Many tumors are characterized by imbalances in sphingolipid metabolism. In many cases, disorders of sphingolipid metabolism are also likely to cause or at least promote cancer. In this review, sphingolipid transport proteins and the processes catalyzed by them are regarded as essential components of sphingolipid metabolism. There is much to suggest that these processes are often rate-limiting steps for metabolism of individual sphingolipid species and thus represent potential target structures for pharmaceutical anticancer research. Here, we summarize empirical and biochemical data on different proteins with key roles in sphingolipid transport and their potential role in cancer.

Plant lipid transfer proteins and homologues of the main birch pollen allergen Bet v 1 are involved in the development of allergic reactions of varying severity to plant foods and pollen. In this study, the sera from patients with tree and weed pollen allergies in the Moscow region were examined. The levels of IL-4, IL-5, IL-9, IL-10, IL-13, IL-17A, IFNγ, TNFα, and TNFβ cytokines were determined in the sera of patients with specific IgE antibodies to Bet v 1 and Pru p 3 allergens. It was confirmed that patients with pollen allergy are often characterized by Th2 response of the immune system, though other mechanisms of allergy development occurred in some cases. The data obtained demonstrate the necessity of detailed analysis of the individual mechanism of allergic reactions and patient-centered approach to the personalized allergy treatment.

Allergies are a widespread problem in western countries, affecting a large part of the population, with levels of prevalence increasingly rising due to reasons still not understood. Evidence accumulated in recent years points to an essential role played by ligands of allergen proteins in the sensitization phase of allergies. In this regard, we recently identified the natural ligand of Pru p 3, a lipid transfer protein, a major allergen from peach fruit and a model of food allergy. The ligand of Pru p 3 has been shown to play a key role in the sensitization to peach and to other plant food sources that provoke cross-reactivity in a large proportion of patients allergic to peach. However, the question of which is the binding pose of this ligand in its carrier protein, and how it can be transferred to receptors of the immune system where it develops its function as a coadjuvant was not elucidated. In this work, different molecular dynamics simulations have been considered as starting points to study the properties of the ligand⁻protein system in solution. Besides, an energy landscape based on collective variables that describe the process of ligand motion within the cavity of Pru p 3 was obtained by using well-tempered metadynamics. The simulations revealed the differences between distinct binding modes, and also revealed important aspects of the motion of the ligand throughout its carrier protein, relevant to its binding⁻unbinding process. Our findings are potentially interesting for studying protein⁻ligand systems beyond the specific case of the allergen protein dealt with here.

Rice growth and productivity is adversely affected by low-temperature stress. From a previous screen of diverse rice genotypes for cold tolerance parameters at the vegetative stage, we selected the tolerant Nipponbare and M202 genotypes and sensitive Cypress and Secano do Brazil genotypes for further analysis at the reproductive stage for physiological and yield parameters. Cold stress severely affected grain yield as estimated by the number of grain per panicle, panicle length, and 100 seed weight. Analysis of gene expression of 21 genes involved in physiological responses to low temperature tested, in the flag leaf and inflorescence tissue of these genotypes, showed an increased expression of the Lipid Transfer Protein genes LTP7 and LTP10 in flag leaf tissue of the tolerant Nipponbare and M202, along with a significant increase in the relative expression of stress-responsive transcription factors (TFs) and cold-inducible genes. In flag leaf tissue OsNAC9, OsNAC10 and OsNAP genes showed high correlation with photosynthesis, stomatal conductance, transpiration and Quantum Efficiency of PSII. In consequence of the foregoing results, we conclude that Nipponbare and M202 are cold tolerant genotypes and that LTP7, LTP10, OsNAC9, OsNAC10 and OsNAP genes can be used as markers in screening for cold tolerance at the reproductive stage. Furthermore based on the results we propose a model of low-temperature tolerance mechanism of how stress is perceived, and how the signal cascade acts to promote tolerance at below-ideal temperatures.

Non-specific lipid transfer proteins (LTPs) are involved in the transport of lipophilic compounds to the cuticular surface in epidermal cells and in the defence against pathogens. The role of glycophosphatidylinositol (GPI)-anchored LTPs (LTPGs) in resistance against non-host mildews in Arabidopsis thaliana was investigated using reverse genetics. Loss of either LTPG1, LTPG2, LTPG5 or LTPG6 increased the susceptibility to penetration of the epidermal cell wall by Blumeria graminis f. sp. hordei (Bgh). However, no impact on pre-penetration defence against another non-host mildew, Erysiphe pisi (Ep), was observed. LTPG1 was localized to papillae at the sites of Bgh penetration. This study shows that, in addition to the previously known functions, LTPGs contribute to pre-invasive defence against certain non-host powdery mildew pathogens., (© 2018 BSPP and John Wiley & Sons Ltd.)

Introduction: Lipid transfer proteins (LTPs) are panallergens found in many plant foods. They are a common cause of food-induced anaphylaxis (FIA) in adults living in the Mediterranean area. LTPs have also been proposed as a main cause of food-dependent exercise-induced anaphylaxis (FDEIA)., Objectives: Describe clinical characteristics and allergen sensitization profiles in patients with FIA related to LTP., Materials and Methods: Forty-three patients were included, aged 3-52 years with a clinical history of FIA and proven sensitization to LTP. Patients were tested with a multiple plant food and pollen panel and specific IgE to LTP allergens. LTP sensitization was assessed by in vivo (Pru p 3, LTP extract) and/or by in vitro tests (specific IgE, ImmunoCAP/ISAC ® )., Results: Median age of first anaphylactic episode was 24 years (range 2-51), 44% had asthma, 74% were atopic and 42% had pollinosis (olive, mugwort, plane tree, wall pellitory and cypress). Co-sensitization to profilins was found in 22%. Overall in our center, LTP-induced anaphylaxis represents 17% of all causes of FIA. Foods implicated in anaphylactic reactions were: fresh fruits 51%, tree nuts 42%, vegetables (including peanut) 40% and seeds 14%. Seven patients had FDEIA., Conclusions: LTPs are important allergens of FIA in Portugal. Clinical reactivity to several taxonomically unrelated plant foods may raise suspicion toward LTP sensitization. The association of LTP-induced anaphylaxis with pollinosis is relevant in our country. The unpredictable clinical expression depends on the effect of cofactors such as exercise. The management of avoidance plans can be challenging due to LTP being a widely cross-reacting allergen in plant foods., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Sterols are essential components of cellular membranes and shape their biophysical properties. The recently discovered family of Lipid transfer proteins Anchored at Membrane contact sites (LAMs) has been suggested to carry out intracellular sterol traffic using StART-like domains. Here, we studied the second StART-like domain of Lam4p from S. cerevisiae by NMR. We show that NMR data are consistent with the StART-like domain structure, and that several functionally important regions within the domain exhibit significant conformational dynamics. NMR titration experiments confirm sterol binding to the canonical sterol-binding site and suggest a role of membrane interactions on the thermodynamics and kinetics of sterol binding., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Lipids are the major constituents of all cell membranes and play dynamic roles in organelle structure and function. Although the spontaneous transfer of lipids between different membranes rarely occurs, lipids are appropriately transported between different organelles for their metabolism and to exert their functions in living cells. Proteins that have the biochemical capability to catalyze the intermembrane transfer of lipids are called lipid transfer proteins (LTPs). All organisms possess many types of LTPs. Recent studies revealed that LTPs are key players in the interorganelle transport of lipids at organelle membrane contact sites (MCSs). This chapter depicts how LTPs rationally operate at MCSs by using the ceramide transport protein CERT as a typical model for the LTP-mediated interorganelle transport of lipids.

Our lack of full understanding of transport and sequestration of the heterologous products currently limit metabolic engineering in plants for the production of high value terpenes. For instance, although all genes of the artemisinin/arteannuin B (AN/AB) biosynthesis pathway (AN-PW) from Artemisia annua have been identified, ectopic expression of these genes in Nicotiana benthamiana yielded mostly glycosylated pathway intermediates and only very little free (dihydro)artemisinic acid [(DH)AA]. Here we demonstrate that Lipid Transfer Protein 3 (AaLTP3) and the transporter Pleiotropic Drug Resistance 2 (AaPDR2) from A. annua enhance accumulation of (DH)AA in the apoplast of N. benthamiana leaves. Analysis of apoplast and cell content and apoplast exclusion assays show that AaLTP3 and AaPDR2 prevent reflux of (DH)AA from the apoplast back into the cells and enhances overall flux through the pathway. Moreover, AaLTP3 is stabilized in the presence of AN-PW activity and co-expression of AN-PW+AaLTP3+AaPDR2 genes yielded AN and AB in necrotic N. benthamiana leaves at 13 days post-agroinfiltration. This newly discovered function of LTPs opens up new possibilities for the engineering of biosynthesis pathways of high value terpenes in heterologous expression systems., (Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

The biosynthesis of glucosylceramide (GlcCer) is a key rate-limiting step in complex glycosphingolipid (GSL) biosynthesis. To further define interacting partners of GlcCer, we have made a cleavable, biotinylated, photoreactive GlcCer analog in which the reactive nitrene is closely apposed to the GlcCer head group, by substituting the native fatty acid with d, l-2-aminohexadecanoic acid. Two amino-GlcCer diastereomer cross-linkers (XLA and XLB) were generated. XLB proved an effective lactosylceramide (LacCer) synthase substrate while XLA was inhibitory. Both probes specifically bound and cross-linked the GlcCer binding protein, glycolipid transfer protein (GLTP), but not other GSL binding proteins (Shiga toxin and cholera toxin). GlcCer inhibited GLTP cross-linking. Both GlcCer cross-linkers competed with microsomal nitrobenzoxadiazole (NBD)-GlcCer anabolism to NBD-LacCer. GLTP showed marked, ATP-dependent enhancement of cell-free intact microsomal LacCer synthesis from endogenous or exogenous liposomal GlcCer, supporting a role in the transport/membrane translocation of cytosolic and extra-Golgi GlcCer. GLTP was specifically labeled by either XLA or XLB GlcCer cross-linker during this process, together with a (the same) small subset of microsomal proteins. These cross-linkers will serve to probe physiologically relevant GlcCer-interacting cellular proteins., (Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.)

Objectives: To establish an efficient expression system for a fusion protein GST-pgLTP (Lipid Transfer Protein) and to test its antifungal activity., Results: The nucleotide sequence of LTP gene was obtained from Panax ginseng using RT-PCR. The ORF of the cDNA is 363 bp, codING for a protein OF 120 amino acids with a calculated MW of 12.09 kDa. The pgLTP gene with a His6-tag at the C-terminus was cloned into the pGEX-6p1 vector to generate a GST-fusion pgLTP protein construct that was expressed in Escherichia coli Rosetta. Following purification by Ni-NTA, the fusion protein exhibited antifungal activity against five fungi found in ginseng., Conclusion: The fusion protein GST-pgLTP has activity against a broad spectrum of phytopathogenic fungi, and can potentially be adapted for production to combat fungal diseases that affect P. ginseng.

Mammalian tribbles homolog 1 (TRIB1) is a human locus that has been shown to significantly impact plasma lipid levels across several ethnic groups. In addition, the gene has been associated with the occurrence of nonalcoholic fatty liver disease. In the present study, a yeast-two-hybrid system was used to screen for novel molecular targets of TRIB1 binding. Loci corresponding to clones that were positive for TRIB1 binding subsequently were assessed for roles in lipid metabolism in mice using adenoviral constructs to induce knockdown or overexpression. Sin3A-associated protein, 18 kDa (SAP18) was identified as a novel binding partner of TRIB1. Knockdown of the Sap18 in mouse liver decreased plasma lipid levels and increased hepatic lipid levels; SAP18 overexpression showed the opposite effects. Transcriptome analysis of the mouse liver revealed that Sap18 knockdown decreased and SAP18 overexpression increased microsomal TG transfer protein (MTTP) expression levels. Chromatin immunoprecipitation analysis showed that halo-tagged SAP18, halo-tagged TRIB1, and anti-mSin3A antibody enriched precipitates for regulatory sequences of the MTTP gene. Enforced expression of SAP18 enhanced and SAP18 knockdown conversely attenuated the enrichment of MTTP regulatory sequences seen with anti-mSin3A antibody. These studies indicated that SAP18 expression enhanced the recruitment of mSin3A in coordination with TRIB1 to MTTP regulatory elements and increased MTTP expression., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background: Lipid transfer protein (LTP) is a widely cross-reacting allergen in plant foods., Objective: To assess whether IgE to vegetable foods show predictable trends in LTP allergic patients., Methods: Clinical allergy to plant foods other than peach was sought in 15 consecutive peach-allergic adults monosensitized to LTP. IgE specific for peach, apple, hazelnut, walnut, peanut, lentil, maize, soybean, tomato, sesame, mustard melon, kiwi, and celery as well as to mugwort pollen was measured., Results: Peach-specific IgE levels exceeded IgE to all other study foods. The higher were peach-specific IgE levels, the higher was the probability that other plant-derived foods scored positive. Mean IgE levels specific for all study foods were strongly correlated to peach specific IgE. Food-specific IgE followed a rather precise hierarchy, both in terms of number of positive in-vitro tests and of IgE levels, with apple at the second place after peach, followed by walnut, hazelnut, peanut, lentil, maize, soybean, tomato, kiwi, sesame, mustard, melon, and celery. Such hierarchy was not necessarily paralleled by clinical allergy as lentil, maize, and soybean scored positive in the majority of patients, but induced allergy in 0, 1, and 0 patients, respectively. IgE levels were not necessarily correlated with the severity of clinical allergy. Little or no IgE reactivity to mugwort pollen was found., Conclusions: In LTP syndrome, IgE reactivity to foods other than peach is in most cases predictable and follows a regular sequence that probably depends on the degree of homology with Pru p3. The reasons why some foods are tolerated by most patients despite elevated IgE reactivity remains to be elucidated.

Historically, cellular trafficking of lipids has received much less attention than protein trafficking, mostly because its biological importance was underestimated, involved sorting and translocation mechanisms were not known, and analytical tools were limiting. This has changed during the last decade, and we discuss here some progress made in respect to mitochondria and the trafficking of phospholipids, in particular cardiolipin. Different membrane contact site or junction complexes and putative lipid transfer proteins for intra- and intermembrane lipid translocation have been described, involving mitochondrial inner and outer membrane, and the adjacent membranes of the endoplasmic reticulum. An image emerges how cardiolipin precursors, remodeling intermediates, mature cardiolipin and its oxidation products could migrate between membranes, and how this trafficking is involved in cardiolipin biosynthesis and cell signaling events. Particular emphasis in this review is given to mitochondrial nucleoside diphosphate kinase D and mitochondrial creatine kinases, which emerge to have roles in both, membrane junction formation and lipid transfer., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This work reports analysis of lipid transfer protein (LTPs) mRNA levels in rat soleus muscle after 12-h and 14-day hindlimb suspension (HS). The LTP genes of interest were as follows: ceramide transporter 1 (CERT1), ceramide-1-phosphate transporter protein (CPTP), sphingosine-1-phosphate transporter (Protein spinster homolog 2—SPNS2), four-phosphate adaptor protein 2 (FAPP2) transferring glucosylceramide, and oxysterol-binding proteins OSBP and ORP4 (family I of OSBP-related proteins). LTP mRNA expression was analyzed using RT-PCR. Early changes in the expression of LTP genes after 12-h HS were characterized by the dramatic decrease in mRNA content of CERT1, CPTP, SPNS2 and ORP4 genes. In contrast, the expression of the FAPP2 gene was increased, whereas OSBP mRNA content did not change as compared to the control level. After the 14-day HS only CERT1 and CPTP mRNA levels remained decreased while expression of other LTP genes did not significantly differ from the control values. Clomipramine treatment did not affect sphingolipid transporters and OSBPs at the early period of HS, but notably enhanced the expression of CERT1, CPTP, FAPP2, and both OSBPs genes in soleus muscle of rats subjected to 14-day unloading. Our data indicate that short-term and long-term muscle unloading differently affects the expression of genes encoding LTPs for sphingolipid and cholesterol intracellular transport. Only ceramide and ceramide-1-phosphate transporters were decreased at both periods of disuse. Taking into account our previous data about acid sphingomyelinase (aSMase) and ceramide up-regulation in the unloaded soleus muscle, as well as a normalizing effect of clomipramine on both high ceramide level and low expression of its transporters at 14-day HS, we can assume that there must be a feedback mechanism in regulation of CERT1 and CPTP genes expression in case of ceramide accumulation caused by disuse. [ABSTRACT FROM AUTHOR]

The lipid phosphatidylinositol 4-phosphate (PI4P) plays a master regulatory role at Golgi membranes, orchestrating membrane budding, non-vesicular lipid transport and membrane organization. It follows that harmonious Golgi function requires strictly maintained PI4P homeostasis. One of the most abundant PI4P effector proteins is the oxysterol binding protein (OSBP), a lipid transfer protein that exchanges trans-Golgi PI4P for ER cholesterol. Although this protein consumes PI4P as part of its lipid anti-porter function, whether it actively contributes to Golgi PI4P homeostasis has been questioned. Here, we employed a series of acute and chronic genetic manipulations, together with orthogonal targeting of OSBP, to interrogate its control over Golgi PI4P abundance. Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in PI4P levels. Additionally, we observe that OSBP has a high capacity for PI4P turnover, even at orthogonal organelle membranes. However, despite also visiting the plasma membrane, endogenous OSBP makes no impact on PI4P levels in this compartment. We conclude that OSBP is a major determinant of Golgi PI4P homeostasis. [ABSTRACT FROM AUTHOR]

Membrane contact sites, where two organelles are in close proximity, are critical regulators of cellular membrane homeostasis, with roles in signaling, lipid metabolism, and ion dynamics. A growing catalog of specialized lipid transfer proteins carry out lipid exchange at these sites. Currently characterized eukaryotic lipid transport proteins are shuttles that typically extract a single lipid from the membrane of the donor organelle, solubilize it during transport through the cytosol, and deposit it in the acceptor organelle membrane. Here, we highlight the recently identified chorein_N family of lipid transporters, including the Vps13 proteins and the autophagy protein Atg2. These are elongated proteins that, distinct from previously characterized transport proteins, bind tens of lipids at once. They feature an extended channel, most likely lined with hydrophobic residues. We discuss the possibility that they are not shuttles but instead are bridges between membranes, with lipids traversing the cytosol via the hydrophobic channel. [ABSTRACT FROM AUTHOR]

Patients with wheat flour food allergy and with baker’s asthma are not sensitised to wheat pollen, despite the fact that they share some common allergens. In the same way, asthmatic bakers tolerate the ingestion of bread. The difference in sensitisation routes (inhalation versus ingestion) and allergenic source (wheat flour versus processed wheat foodstuffs) could explain this fact, although some wheat allergens, like α-amylase inhibitors, lipid transfer proteins and gliadin are implicated in both types of allergy. We report the case of a 45-year-old male who worked in a bakery for 30 years as a baker. He was confirmed to have occupational asthma, rhinitis and food allergy due to wheat flour. [ABSTRACT FROM AUTHOR]

Oxysterol binding protein-related protein 2 (ORP2) is a lipid binding protein that has been implicated in various cellular processes, including lipid sensing, cholesterol efflux, and endocytosis. We recently identified ORP2 as a member of a protein complex that regulates glucocorticoid biosynthesis. Herein, we examine the effect of silencing ORP2 on adrenocortical function and show that the ORP2 knockdown cells exhibit reduced amounts of multiple steroid metabolites, including progesterone, 11-deoxycortisol, and cortisol, but have increased concentrations of androgens, and estrogens. Moreover, silencing ORP2 suppresses the expression of most proteins required for cortisol production and reduces the expression of steroidogenic factor 1 (SF1). ORP2 silencing also increases cellular cholesterol, concomitant with decreased amounts of 22-hydroxycholesterol and 7-ketocholesterol, two molecules that have been shown to bind to ORP2. Further, we show that ORP2 binds to liver X receptor (LXR) and is required for nuclear LXR expression. LXR and ORP2 are recruited to the CYP11B1 promoter in response to cAMP signaling. Additionally, ORP2 is required for the expression of other LXR target genes, including ABCA1 and the LDL receptor (LDLR). In summary, we establish a novel role for ORP2 in regulating steroidogenic capacity and cholesterol homeostasis in the adrenal cortex. [ABSTRACT FROM AUTHOR]

Lipid transfer proteins (LTPs) are recognized as key players in the inter-organelle trafficking of lipids and are rapidly gaining attention as a novel molecular target for medicinal products. In mammalian cells, ceramide is newly synthesized in the endoplasmic reticulum (ER) and converted to sphingomyelin in the trans-Golgi regions. The ceramide transport protein CERT, a typical LTP, mediates the ER-to-Golgi transport of ceramide at an ER-distal Golgi membrane contact zone. About 20 years ago, a potent inhibitor of CERT, named (1R,3S)-HPA-12, was found by coincidence among ceramide analogs. Since then, various ceramide-resembling compounds have been found to act as CERT inhibitors. Nevertheless, the inevitable issue remains that natural ligand-mimetic compounds might directly bind both to the desired target and to various undesired targets that share the same natural ligand. To resolve this issue, a ceramide-unrelated compound named E16A, or (1S,2R)-HPCB-5, that potently inhibits the function of CERT has recently been developed, employing a series of in silico docking simulations, efficient chemical synthesis, quantitative affinity analysis, protein–ligand co-crystallography, and various in vivo assays. (1R,3S)-HPA-12 and E16A together provide a robust tool to discriminate on-target effects on CERT from off-target effects. This short review article will describe the history of the development of (1R,3S)-HPA-12 and E16A, summarize other CERT inhibitors, and discuss their possible applications. [ABSTRACT FROM AUTHOR]