scholarly journals Phosphorylation of LCB1 subunit of serine palmitoyltransferase stimulates its activity and modulates sphingolipid biosynthesis in Arabidopsis

2020 ◽  
Author(s):  
Yuan Li ◽  
Hanwei Cao ◽  
Tingting Dong ◽  
Xiaoke Wang ◽  
Liang Ma ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
De Novo ◽  
Membrane Lipid ◽  
Signal Molecules ◽  
Serine Palmitoyltransferase ◽  
Cellular Processes ◽  
Molecular Pattern ◽  
Long Chain Base ◽  
Rate Limiting ◽  
Sphingolipid Biosynthesis

Abstract Sphingolipids are the structural elements for membrane lipid bilayers and the signal molecules for many cellular processes. Serine palmitoyltransferase (SPT) is the first committed and rate-limiting enzyme in the de novo sphingolipids biosynthetic pathway. The core SPT was previously suggested as a heterodimer consisting of LCB1 and LCB2 subunits. The SPT activity was shown to be inhibited by orosomucoid proteins (ORMs) and stimulated by small subunits of SPT (ssSPT). However, whether LCB1 is modified and how the modification regulates SPT activity have been unclear. Here, we show that activation of MPK3 and MPK6 by upstream MKK9 and Flg22 (a pathogen-associated molecular pattern) treatment increases SPT activity and induces the accumulation of sphingosine long-chain base (LCB) t18:0 in Arabidopsis thaliana; the activated MPK3 and MPK6 phosphorylate AtLCB1. Phosphorylation of AtLCB1 strengthens its binding with AtLCB2b, promotes its binding with ssSPTs, and stimulates the higher-order-oligomer and active SPT complexes formation. Our findings suggest a novel regulatory mechanism of SPT activity.

Regulation of de novo sphingolipid biosynthesis and the toxic consequences of its disruption

2001 ◽  
Vol 29 (6) ◽  
pp. 831-835 ◽  
Author(s):  
S. C. Linn ◽  
H. S. Kim ◽  
E. M. Keane ◽  
L. M. Andras ◽  
E. Wang ◽  
...  
Keyword(s):  
De Novo ◽  
Uv Light ◽  
Wide Spectrum ◽  
Sphingolipid Metabolism ◽  
Intrinsic Activity ◽  
Type I ◽  
Serine Palmitoyltransferase ◽  
Post Translational Modification ◽  
Sphingolipid Biosynthesis ◽  
Complex Sphingolipids

Complex sphingolipids are ‘built’ on highly bio-active backbones (sphingoid bases and ceramides) that can cause cell death when the amounts are elevated by turnover of complex sphingolipids, disruption of normal sphingolipid metabolism, or over-induction of sphingolipid biosynthesis de novo. Under normal conditions, it appears that the bioactive intermediates of this pathway (3-keto-sphinganine, sphinganine and ceramides) are kept at relatively low levels. Both the intrinsic activity of serine palmitoyltransferase (SPT) and the availability of its substrates (especially palmitoyl-CoA) can have toxic consequences for cells by increasing the production of cytotoxic intermediates. Recent work has also revealed that diverse agonists and stresses (cytokines, UV light, glucocorticoids, heat shock and toxic compounds) modulate SPT activity by induction of SPTLC2 gene transcription and/or post-translational modification. Mutation of the SPTLC1 component of SPT has also been shown to cause hereditary sensory neuropathy type I, possibly via aberrant oversynthesis of sphingolipids. Another key step of the pathway is the acylation of sphinganine (and sphingosine in the recycling pathway) by ceramide synthase, and up-regulation of this enzyme (or its inhibition to cause accumulation of sphinganine) can also be toxic for cells. Since it appears that most, if not all, tissues synthesize sphingolipids de novo, it may not be surprising that disruption of this pathway has been implicated in a wide spectrum of disease.

scholarly journals Crassaostrea gigas Oyster Shell Extract Inhibits Lipogenesis via Suppression of Serine Palmitoyltransferase

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000
Author(s):  
Nguyen Khoi Song Tran ◽  
Jeong Eun Kwon ◽  
Se Chan Kang ◽  
Soon-Mi Shim ◽  
Tae-Sik Park
Keyword(s):  
De Novo ◽  
Preventive Measure ◽  
Ethanol Extract ◽  
Oyster Shell ◽  
Lipid Lowering ◽  
Metabolic Dysfunction ◽  
Serine Palmitoyltransferase ◽  
Lipogenic Gene Expression ◽  
Cholesterol Levels ◽  
Sphingolipid Biosynthesis

Oysters are widely consumed seafood, but their shells impose a serious environmental problem. To extend the utilization of oyster shell waste, we investigated the biological role of oyster shell extract. In this study, we verified that the ethanol extract of oyster shell (EOS) contains taurine and betaine, the major components of oyster body. EOS downregulated transcription of Sptlc1 and Sptlc2 mRNA, the subunits of serine palmitoyltransferase (SPT). Suppression of SPT subunits reduced sphinganine and sphingomyelin by inhibiting de novo sphingolipid biosynthesis. Inhibition of sphingomyelin biosynthesis resulted in downregulation of lipogenic gene expression such as ACC, FAS, SCD1, and DGAT2. Consistent with inhibition of lipogenesis, cellular triglyceride levels were diminished by EOS, but cholesterol levels were not altered. Taken together, these results suggest that EOS has a lipid-lowering effect and could be applied as either a therapeutic or preventive measure for metabolic dysfunction.

scholarly journals Rescue of cell growth by sphingosine with disruption of lipid microdomain formation in Saccharomyces cerevisiae deficient in sphingolipid biosynthesis

2006 ◽  
Vol 394 (1) ◽  
pp. 237-242 ◽  
Author(s):  
Motohiro Tani ◽  
Akio Kihara ◽  
Yasuyuki Igarashi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Growth ◽  
Serine Palmitoyltransferase ◽  
Kinase Gene ◽  
Yeast Saccharomyces Cerevisiae ◽  
Long Chain Base ◽  
Triton X ◽  
Lipid Microdomain ◽  
Sphingolipid Biosynthesis ◽  
Complex Sphingolipids

In the yeast Saccharomyces cerevisiae, sphingolipids are essential for cell growth. Inactivation of sphingolipid biosynthesis, such as by disrupting the serine palmitoyltransferase gene (LCB2), is lethal, but cells can be rescued by supplying an exogenous LCB (long-chain base) like PHS (phytosphingosine) or DHS (dihydrosphingosine). In the present study, supplying SPH (sphingosine), an unnatural LCB for yeast, similarly rescued the Δlcb2 cells, but only when SPH 1-phosphate production was inhibited by deleting the LCB kinase gene LCB4. Exogenously added SPH was adequately converted into phosphoinositol-containing complex sphingolipids. Interestingly, cells carrying SPH-based sphingolipids exhibited a defect in the association of Pma1p with Triton X-100-insoluble membrane fractions, and displayed sensitivities to both Ca2+ and hygromycin B. These results suggest that the SPH-based sphingolipids in these cells have properties that differ from those of the PHS- or DHS-based sphingolipids in regard to lipid microdomain formation, leading to abnormal sensitivities towards certain environmental stresses. The present paper is the first report showing that in sphingolipid-deficient S. cerevisiae, the requirement for LCB can be fulfilled by exogenous SPH, although this supplement results in failure of lipid microdomain formation.

Intestinal aspects of lipid absorption: in review

1989 ◽  
Vol 67 (3) ◽  
pp. 179-191 ◽  
Author(s):  
A. B. R. Thomson ◽  
M. Keelan ◽  
M. L. Garg ◽  
M. T. Clandinin
Keyword(s):  
Dietary Fat ◽  
De Novo ◽  
Membrane Lipid ◽  
Dietary Fats ◽  
Lipid Absorption ◽  
Limiting Factor ◽  
Adaptive Responses ◽  
Phospholipid Biosynthesis ◽  
New Knowledge ◽  
Rate Limiting

The rapidly evolving field of lipid absorption is reviewed with the thrust of new knowledge focused on the interpendency of the luminal and cellular phases of absorption. To date little attention has been paid to factors that regulate the phospholipid biosynthesis in the enterocyte. The availability of 20:4ω6 may be the rate-limiting factor for phospholipid synthesis. The source of 20:4ω6 is unknown, whether it be synthesized de novo the enterocyte or entirely originating from degradation of bile phospholipid. It has been established that dietary fat can modulate the enterocyte membrane lipid composition and transport properties. Specified fats such as as fish oils rich in 20:5ω3 and 22:6ω3 have been implicated as protective against hypercholesterolemia. However, the effects of these dietary fats on the transport of nutrients across the enterocyte are not yet known, nor are the mechanisms responsible for the adaptive responses of the brush border identified.

scholarly journals Viral serine palmitoyltransferase induces metabolic switch in sphingolipid biosynthesis and is required for infection of a marine alga

2016 ◽  
Vol 113 (13) ◽  
pp. E1907-E1916 ◽  
Author(s):  
Carmit Ziv ◽  
Sergey Malitsky ◽  
Alaa Othman ◽  
Shifra Ben-Dor ◽  
Yu Wei ◽  
...  
Keyword(s):  
De Novo ◽  
Serine Palmitoyltransferase ◽  
Metabolic Switch ◽  
Marine Viruses ◽  
Key Enzyme ◽  
Infected Cells ◽  
Biochemical Analyses ◽  
Biological Entities ◽  
Sphingolipid Biosynthesis

Marine viruses are the most abundant biological entities in the oceans shaping community structure and nutrient cycling. The interaction between the bloom-forming algaEmiliania huxleyiand its specific large dsDNA virus (EhV) is a major factor determining the fate of carbon in the ocean, thus serving as a key host-pathogen model system. The EhV genome encodes for a set of genes involved in the de novo sphingolipid biosynthesis, not reported in any viral genome to date. We combined detailed lipidomic and biochemical analyses to characterize the functional role of this virus-encoded pathway during lytic viral infection. We identified a major metabolic shift, mediated by differential substrate specificity of virus-encoded serine palmitoyltransferase, a key enzyme of sphingolipid biosynthesis. Consequently, unique viral glycosphingolipids, composed of unusual hydroxylated C17 sphingoid bases (t17:0) were highly enriched in the infected cells, and their synthesis was found to be essential for viral assembly. These findings uncover the biochemical bases of the virus-induced metabolic rewiring of the host sphingolipid biosynthesis during the chemical “arms race” in the ocean.

Membrane lipid biogenesis and transport

1986 ◽  
Vol 44 ◽  
pp. 70-71
Author(s):  
E.A. Dawidowicz
Keyword(s):  
Lipid Bilayers ◽  
De Novo ◽  
Membrane Lipids ◽  
Essential Feature ◽  
Liver Microsomes ◽  
Eukaryotic Cell ◽  
Membrane Lipid ◽  
Membrane Components ◽  
Isolated Liver ◽  
Initial Assembly

Membrane biogenesis is an essential feature of cellular development and growth. The initial assembly of membrane lipids and proteins occurs primarily in the endoplasmic reticulum (ER). It has been demonstrated that the enzymes involved in the de novo biosynthesis of phospholipids are exclusively located on the cytoplasmic surface of the ER. A rapid transbilayer movement of phospholipids has also been reported in isolated liver microsomes, which is compatible with the movement of newly synthesized lipids to the lumenal surface of the ER. Comparison with the transbilayer movement of phospholipids across protein-free lipid bilayers, has lead to the proposal that a protein which would catalyze the translocation of phospholipids across the ER membrane (“flipase”), might be involved in the assembly of the lipid bilayer of the ER. Since the various membranes in a eukaryotic cell differ markedly in their lipid composition, it is clear that specific sorting and transport of these membrane components must occur.

scholarly journals A genome-wide CRISPR/Cas9 screen reveals that the aryl hydrocarbon receptor stimulates sphingolipid levels

2020 ◽  
Vol 295 (13) ◽  
pp. 4341-4349 ◽  
Author(s):  
Saurav Majumder ◽  
Mari Kono ◽  
Y. Terry Lee ◽  
Colleen Byrnes ◽  
Cuiling Li ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Hela Cells ◽  
Knockout Mice ◽  
Biosynthetic Pathway ◽  
De Novo ◽  
Serine Palmitoyltransferase ◽  
Aryl Hydrocarbon ◽  
Genome Wide ◽  
A Genome ◽  
Sphingolipid Biosynthesis

Sphingolipid biosynthesis generates lipids for membranes and signaling that are crucial for many developmental and physiological processes. In some cases, large amounts of specific sphingolipids must be synthesized for specialized physiological functions, such as during axon myelination. How sphingolipid synthesis is regulated to fulfill these physiological requirements is not known. To identify genes that positively regulate membrane sphingolipid levels, here we employed a genome-wide CRISPR/Cas9 loss-of-function screen in HeLa cells using selection for resistance to Shiga toxin, which uses a plasma membrane-associated glycosphingolipid, globotriaosylceramide (Gb3), for its uptake. The screen identified several genes in the sphingolipid biosynthetic pathway that are required for Gb3 synthesis, and it also identified the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor widely involved in development and physiology, as being required for Gb3 biosynthesis. AHR bound and activated the gene promoter of serine palmitoyltransferase small subunit A (SPTSSA), which encodes a subunit of the serine palmitoyltransferase that catalyzes the first and rate-limiting step in de novo sphingolipid biosynthesis. AHR knockout HeLa cells exhibited significantly reduced levels of cell-surface Gb3, and both AHR knockout HeLa cells and tissues from Ahr knockout mice displayed decreased sphingolipid content as well as significantly reduced expression of several key genes in the sphingolipid biosynthetic pathway. The sciatic nerve of Ahr knockout mice exhibited both reduced ceramide content and reduced myelin thickness. These results indicate that AHR up-regulates sphingolipid levels and is important for full axon myelination, which requires elevated levels of membrane sphingolipids.

Increased Expression of Serine Palmitoyltransferase (SPT) in Balloon-injured Rat Carotid Artery

2001 ◽  
Vol 86 (11) ◽  
pp. 1320-1326 ◽  
Author(s):  
Jill Carton ◽  
Dennis Argentieri ◽  
Bruce Damiano ◽  
Michael D’Andrea ◽  
David Uhlinger
Keyword(s):  
Vascular Injury ◽  
Potential Role ◽  
De Novo ◽  
Serine Palmitoyltransferase ◽  
Proliferating Cells ◽  
Wound Healing Response ◽  
Complex Wound ◽  
Functional Consequences ◽  
Sphingolipid Biosynthesis

SummaryThe response to vascular injury is a complex wound healing response involving cell proliferation, migration, remodeling and inflammation. In the present studies we employed a rat balloon angioplasty model of vascular injury to investigate the potential role of sphingolipid signaling in the response to vascular injury. The enzyme serine palmitoyltransferase (SPT) catalyzes the first committed step in de novo sphingolipid biosynthesis. We observed marked upregulation of expression of both SPT subunits in actively proliferating cells in injured vessels. This enhanced SPT expression occurs in de-differentiated fibroblasts and proliferating vascular smooth muscle cells. The upregulation is particularly apparent in the proliferating luminal edge of the neointima and the adventitial de-differentiated fibroblasts and may serve as a hallmark of this process. The possible functional consequences of this enzyme upregulation and its role in the response to vascular injury are suggested but remain to be determined.

scholarly journals Phytosphingosine induces systemic acquired resistance through activation of sphingosine kinase

2020 ◽  
Author(s):  
So Yeon Seo ◽  
Yu Jung Kim ◽  
Myung Hee Nam ◽  
Ky Young Park
Keyword(s):  
Systemic Acquired Resistance ◽  
De Novo ◽  
Cell Damage ◽  
Plant Immunity ◽  
Acquired Resistance ◽  
Signaling Molecules ◽  
Dependent Manner ◽  
Serine Palmitoyltransferase ◽  
Exogenous Addition ◽  
Sphingolipid Biosynthesis

AbstractPhytosphingosine (PHS) is a naturally occurring bioactive sphingolipid molecule. Intermediates such as sphingolipid long-chain bases (LCBs) in sphingolipid biosynthesis have been shown to have important roles as signaling molecules. In this study, exogenous addition of PHS caused rapid induction of transcripts responsible for transient synthesis of LCBs, reactive oxygen species, and ethylene. These events were followed by the induction of sphingolipid kinase (SphK), which metabolized PHS to phytosphingosine-1-phosphate in an biphasic manner. PHS alleviated not only pathogen-induced cell damage but also reduced the growth of virulent pathogens in the entire upper part of the PHS-treated plant stem during the necrotic stage after inoculation, suggesting the development of systemic acquired resistance (SAR) and plant immunity. Moreover, PHS treatment up-regulated the transcription and activity of SphK, accompanied by prominent increases in the transcription levels of serine palmitoyltransferase (LCB1 and LCB2) for de novo synthesis of sphingolipids, as well as ROS-detoxifying enzymes and PR proteins at 48 h after virulent pathogen infection. The impairment of ROS production at this time is more beneficial for the activation of SphK and inhibition of pathogenicity during the necrotic stage of hemibiotrophic infection, indicating that necrotic cell death at the late stage is regulated by ROS-independent SphK. Phosphorylated LCBs significantly reduced pathogen-induced cell damage. These observations suggest that selective channeling of sphingolipids into phosphorylated forms in a time-dependent manner has a pro-survival effect by promoting SAR in plant immunity.4.One Sentence SummarySelective gene expression in sphingolipid biosynthesis and channeling into their phosphorylated forms are significant determinants of their roles as pro-survival signaling molecules.

scholarly journals The Crucial Roles of Phospholipids in Aging and Lifespan Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yucan Dai ◽  
Haiqing Tang ◽  
Shanshan Pang
Keyword(s):  
Lipid Bilayers ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Mechanisms Of Action ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Lipid Change ◽  
The Relationship ◽  
Signal Transductions ◽  
Phospholipid Species

Phospholipids are major membrane lipids that consist of lipid bilayers. This basic cellular structure acts as a barrier to protect the cell against various environmental insults and more importantly, enables multiple cellular processes to occur in subcellular compartments. Numerous studies have linked the complexity of membrane lipids to signal transductions, organelle functions, as well as physiological processes, and human diseases. Recently, crucial roles for membrane lipids in the aging process are beginning to emerge. In this study, we summarized current advances in our understanding of the relationship between membrane lipids and aging with an emphasis on phospholipid species. We surveyed how major phospholipid species change with age in different organisms and tissues, and some common patterns of membrane lipid change during aging were proposed. Further, the functions of different phospholipid molecules in regulating healthspan and lifespan, as well as their potential mechanisms of action, were also discussed.

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