ViewpointSphingolipids: second messengers, mediators and raft constituents in signaling
Section snippets
Ceramide, a second messenger in lymphocytes
A prototype molecule for the second messenger role of sphingolipids is ceramide. The transition from regarding these molecules as membrane constituents to regarding them as signals is illustrated best in neutrophils, where ceramide accumulates during phagocytosis, particularly as ceramide-1-phosphate (C1P). Elevated levels of this phospholipid promote the fusion of liposomes, which is now attributed to the signaling character, rather than the membrane constituent feature, of C1P. This implies a
Sphingolipids: constituents of signal-initiating rafts
Rafts serve as platforms for glycosylphosphatidylinositol (GPI)-anchored proteins (e.g. CD14, CD16b, CD24, CD48, CD58, CD59, CD67, CD73, CD87 and CD157), some transmembrane proteins [e.g. linker of activated T cells (LAT), CD4, CD8, CD26, CD36 and CD44], receptors [e.g. FceRI, FcaR and the B-cell receptor (BCR)] and doubly acylated protein tyrosine kinases of the Src family (Lyn, Lck, Fyn, Hck; reviewed in Ref. 3). The first two groups are incorporated into rafts in the endoplasmic reticulum
Conclusions and perspectives
Sphingolipids are involved in the initiation and transmission of signals in leukocytes, making them attractive drug candidates. Indeed, derivatives have been used as potential therapeutics for immuno-stimulation (α-galactosylceramide), immuno-suppression (ISP-1 also termed myriocin) and hematopoiesis (N-butyrylsphinganine). In addition, interfering with the enzymes involved in the anabolism and catabolism of sphingolipids might lead to a shift in the balance between counter-regulatory
References (33)
GPI-microdomains: a role in signalling via immunoreceptors
Immunol. Today
(1999)The formation of ceramide-1-phosphate during neutrophil phagocytosis and its role in liposome fusion
J. Biol. Chem.
(1998)- et al.
Ceramide and apoptosis
Trends Biochem. Sci.
(1999) Kinase suppressor of ras is ceramide-activated protein kinase
Cell
(1997)Sphingosine-1-phosphate inhibits activation of caspases that cleave poly(ADP-ribose)polymerase and lamins during Fas- and ceramide-mediated apoptosis in Jurkat T-lymphocytes
J. Biol. Chem.
(1998)BAD enables ceramide to signal apoptosis via Ras and Raf-1
J. Biol. Chem.
(1998)Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate
Cell
(1999)Membrane organization in immunoglobulin E receptor signaling
Curr. Opin. Chem. Biol.
(1999)The anti-ganglioside monoclonal antibody AA4 induces protein tyrosine phosphorylations, but not degranulation, in rat basophilic leukemia cells
J. Biol. Chem.
(1994)Membrane compartmentation is required for efficient T cell activation
Immunity
(1998)
Sphingosine-1-phosphate: extracellular mediator or intracellular second messenger?
Biochem. Pharmacol.
The balance between sphingosine and sphingosine-1-phosphate is decisive for mast cell activation after FceRI triggering
J. Exp. Med.
Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids
Proc. Natl. Acad. Sci. U. S. A.
CD28 signals through acidic sphingomyelinase
J. Exp. Med.
Phosphorylation of Raf by ceramide-activated protein kinase
Nature
Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis
Nature
Cited by (55)
Brain and testicular metabonomics revealed the protective effects of Guilingji on senile sexual dysfunction rats
2022, Journal of EthnopharmacologyCitation Excerpt :Various sphingolipids have important physiological effects on the normal body functions. Sphingolipids are major cell membrane constituents and important precursors of second messengers (Iessi et al., 2020; Prieschl and Baumruke, 2000). Sphingolipid levels can affect cell membrane fluidity, which is strongly related to signal sensitivity and necessary for normal cellular activities.
Elevated functional versatility of the soil microbial community associated with the invader Carpobrotus edulis across a broad geographical scale
2022, Science of the Total EnvironmentLiquid chromatography-tandem mass spectrometry with a new separation mode for rapid profiling of the Z/E isomers of plant glucosylceramides
2021, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :Sphingolipids are complex lipids that contain ceramide, a unique hydrophobic moiety comprising a long-chain base (LCB) and fatty acid (FA) connected via an amide linkage. Sphingolipids are highly diversified among eukaryotic organisms and widely involved in development and various cellular signaling processes [1–5]. Glucosylceramides (GlcCer) are a major class of sphingolipids conserved in eukaryotes.
Membrane-attached mammalian cytochromes P450: An overview of the membrane's effects on structure, drug binding, and interactions with redox partners
2018, Journal of Inorganic BiochemistryCitation Excerpt :Membranes' biophysical properties depend on their composition, so changes in membrane composition can affect many physiologically important processes. The presence of lipid rafts can explain certain aspects of lipids' influence on the behavior of membranes and membrane enzymes [124–129]. Lipid rafts are proposed to be regions with enhanced lipid ordering resulting from elevated levels of cholesterol and saturated lipids [49].
Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites
2017, Journal of Biological ChemistryCitation Excerpt :Sphingolipids are amphipathic lipids consisting of a sphingoid backbone acylated with a long-chain fatty acid and having a polar head group. Although the basic sphingolipid, ceramide, is a secondary signaling molecule involved in, for example, apoptosis (8–10), modified or complex sphingolipids are major components of the outer leaflet of eukaryotic plasma membranes involved, together with sterols, in the formation of microdomains commonly known as lipid rafts. These domains have been proposed to function in a diverse array of processes from the polarized trafficking of lipid-modified proteins to the assembly and activation of signal transduction complexes (11).
Lipid rafts modulate the activation but not the maintenance of store-operated Ca<sup>2+</sup> entry
2010, Biochimica et Biophysica Acta - Molecular Cell Research