Phospholipids containing ether-bound hydrocarbon-chains are essential for efficient phagocytosis and neutral lipids of the ester-type perturb development in Dictyostelium

Abstract

Lipids are the building blocks for cellular membranes; they provide signalling molecules for membrane dynamics and serve as energy stores. One path of their synthesis is initiated by glycerol-3-phosphate acyltransferase (GPAT), which in Dictyostelium resides on the endoplasmic reticulum. When an excess of fatty acids is present, it redistributes to storage organelles, the lipid droplets. Mutants, where the GPAT was eliminated by homologous recombination, produce fewer lipid droplets and are almost devoid of triacylglycerols (TAG), rendering them more resistant to cell death and cell loss in the developmental stages preceding fruiting body formation. The enzyme most closely related to GPAT is called FARAT, because it combines a fatty acyl-reductase (FAR) and an acyltransferase (AT) domain in its sequence. The protein is confined to the lumen of the peroxisome, where it transfers a fatty acid to dihydroxyacetone-phosphate initiating the synthesis of ether lipids, later completed at the endoplasmic reticulum. A mutant lacking FARAT produces lipid droplets that are devoid of the storage lipid monoalkyl-diacyl-glycerol (MDG), but the efficiency of spore formation in the developmental cycle is largely unaltered. Instead, these mutants are strongly impaired in phagocytosis of yeast particles, which is attributed to reduced synthesis of membrane phospholipids containing ether-linked chains.

Complex Sphingolipid Profiling and Identification of an Inositol Phosphorylceramide Synthase inDictyostelium discoideum

“…Our untargeted LC-MS/MS lipidome analyses revealed that, in line with previous studies (27,60), the phospholipid pool in D. discoideum is mostly composed of ether lipids, i.e. lipids with ether-linked acyl-chains that are less abundant in mammals (75,76) and absent in plants or fungi (77).…”

“…2A, Supplemental Table 2). These data are consistent with those reported previously by others (27,60,61). Besides, diacylphospholipids (~ 88.7 mol %), D. discoideum contains substantial amounts of lysophospholipids (~ 6.8 mol %), notably lysophosphatidyl-ethanolamine (LPE), Cers (~ 0.6 mol %), diacylglycerol (DAG, ~ 2.3 mol %) and triacylglycerols (TAG; ~ 1.6 mol %) (Fig.…”

“…Apart from its importance for infection research, D. discoideum is also a versatile tool to study the cell biology of lipids. For example, recent work revealed that D. discoideum primarily utilises ether-linked inositol phospholipids for signalling (26) and that ether lipids play an important role during phagocytosis (27). We previously demonstrated that intracellular mycobacteria use D. discoideum triacylglycerols and phospholipids as major carbon and energy source (28,29).…”

Glycerol-3-phosphate acyltransferases and metabolic syndrome: recent advances and future perspectives

“…Besides, GPAT4-deficient mice lack breast milk, making it difficult for pups to survive unless they are replaced or the adoptive mother is changed (Ref. 59). Information about different GPAT subtypes is still limited, and not yet fully understood, so further research is necessary to better understand the physiological and pathological effects of GPAT subtypes.…”

Sulfoquinovosylglyceryl ether, a new group of ether lipids from lake ball‐forming green alga Aegagropilopsis moravica (family Pithophoraceae)

“…Examples include etheric membrane lipids from Archaea, [2] ladderane membrane lipids from anaerobic ammonia-oxidizing (anammox) bacteria, [3] paramecyl alcohol from ciliate Paramecium tetraurelia, [4] diacylglyceryl ether from marine animals, [5] betaine lipids from micro-and macroorganisms except seed-bearing plants or metazoans, [6] plasmalogens, [7] seminolipids, [8] and platelet-activating factor [9] from mammals (Figure 1). The physiological roles of these molecules are yet fully understood, but some are known to be associated with the ability to adapt to extreme environments such as high temperature, low pH, high salinity, [10] and phosphorous deprivation, [11,12] or a variety of biological events including ATP synthesis, [13] establishment of infection, [14] phagocytosis, [15] to acquire buoyance in the deep sea, [16][17][18] spermatogenesis, [19] immunity, [7] neuronal development, [7] lens organization, lens transparency, [20] and for radical scavenging. [7] In mammals, deficiencies in ether lipid biosynthesis cause two serious congenital disorders, rhizomelic chondrodysplasia punctata (RCDP) and Zellweger spectrum disorders, and lower ether lipid levels in serum or tissues are associated with a range of neurological and metabolic diseases [21] including Alzheimer's disease (AD), schizophrenia, Parkinson's disease (PD), Down syndrome, Gaucher disease, Niemann-Pick type C disease, diabetes, cardiovascular disease, and cancer.…”