Gangliosides in Podocyte Biology and Disease
<p>Global view of the sphingolipid metabolism. Simplified representation of the four main pathways encompassing the synthesis of sphingolipid species, with ceramides as central compounds. Plain arrows indicate single reactions. Dashed arrows denote multiple reactions. De novo and sphingomyelin pathways result in ceramide synthesis from palmitic acid and sphingomyelin as ultimate precursors, respectively. The so-called salvage or catabolic pathway results in the production of the bioactive sphingosine-1 phosphate. Ceramide itself can be phosphorylated into the bioactive ceramide-1 phosphate. Finally, the hydrolytic or glycosphingolipid pathway leads to ceramide glycation. Galactosyl-ceramide is the precursor of sulfatides, not shown in the figure. The rest of the complex glycosphingolipids (lactosides, globosides, cerebrosides, and gangliosides) are derived from lactosyl ceramide (LacCer). All pathways are reversible except the de novo synthesis.</p> "> Figure 2
<p>Schematic representation of ganglioside biosynthesis pathways. LacCer are the precursors of the globo, lacto, muco, and ganglio series of glycosphingolipids. GM3 are the precursors of the a, b, and c series of gangliosides. LacCer are precursors of asialo (0-series) gangliosides (GA). GA1 give way to fucosylated glycosphingolipids. “/” denotes two different structures of gangliosides produced from the same precursor. “α” denotes specific ganglioside structures in which one sialic acid residue is branched to N-acetylgalactosamine (GalNAc). All the other sialic acid residues are branched to galactose residues (modified from [<a href="#B5-ijms-21-09645" class="html-bibr">5</a>]). The orange colored rectangles denote the molecular species whose abundance has been reported to date as changed in the context of podocytopathies (summarized in Table 1). Many of these reactions are reversible. GM: Monosialo gangliosides; GD: Disialo gangliosides; GT: Trisialo gangliosides; GQ: Quadrisialo gangliosides; GP: Pentasialo gangliosides.</p> ">
Abstract
:1. An Overview of Sphingolipid and Glycosphingolipid Metabolism
2. Podocytes: A Complex Structure and a Singular Membrane Organization
3. Gangliosides in Podocytes
3.1. O-Acetylated GD3
3.2. GM3 and GD3
3.3. GM2
3.4. GA1
4. Lessons from APOL1 Genetic Variants
5. A Word by Ceramides
6. The Role of the Immune System
7. A Call for Deep Analysis
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
APOL1 | Apolipoprotein L1 |
Asah1 | Lysosomal acid ceramidase |
CMIP | lC-maf inducing protein |
DN | Diabetes-associated nephropathy |
EGF | Epidermal growth factor |
eGFR | Estimated glomerular filtration rate |
ESI | Electrospray ionization |
FSGS | Focal and segmental glomerulosclerosis |
Flt1 | Vascular endothelial growth factor receptor 1 |
GalNAc | N-acetylgalactosamine |
GlcCer | Glucosylceramide |
GA | Asialo gangliosides |
GD | Di-sialo gangliosides |
GM | Mono-syalo gangliosides |
GP | Penta-sialo gangliosides |
GQ | Quadri-sialo gangliosides |
GSL-1 | Glycosphingolipid-1 |
GT | Tri-sialo gangliosides |
HDL | High density lipoproteins |
HPTLC | High performance thin layer chromatography |
INS | Idiopathic nephrotic syndrome |
LacCer | Lactosylceramide |
MALDI | Matrix assisted laser desorption ionization |
MCNS | Minimal change nephotic syndrome |
NEU | Neuraminidase |
PAN | Puromycin aminonucleoside nephropathy |
ST8Sia1 | Ganglioside D3 synthase |
SMPDL3b | Sphingomyelinase-like phosphodiesterase 3b |
ST3Gal1 | alpha-2,3-sialyltransferase |
ST3Gal5 | Ganglioside M3 synthase |
SLE | systemic lupus erythematosus |
TCR | T-cell receptor |
VEGF | Vascular endothelial growth factor |
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Molecular Species | Pathology | Observed Changes | Reference |
---|---|---|---|
Ceramide | APOL1 associated FSGS | (podocytes) | [8] |
Proteinuria model (Asah1 KO mouse) | (lysosomes) | [51] | |
Genetic steroid resistant nephrotic syndrome | (glomeruli) | [54,55,56] | |
Glomerular sclerosis (acid sphingomyelinase overexpression) | (glomeruli) | [59] | |
GlcCer | APOL1 associated FSGS | (podocytes) | [8] |
LacCer | Lupus nephritis | (kidney) | [40] |
APOL1 associated FSGS | (podocytes) | [8] | |
GM3 | INS (CMIP overexpression) | (podocytes) | [7] |
DN (streptozotocin rat model) | (kidney) | [35,36] | |
DN (streptozotocin rat model) | (glomeruli) | [37] | |
DN (type 1 diabetes rat model) | (glomeruli) | [38] | |
DN (mouse model) | (glomeruli) | [39] | |
APOL1 associated FSGS | (podocyte rafts) | [8] | |
Lupus nephritis (mouse model) | (kidney) | [41] | |
IgA nephropathy, Henoch-Schönlein purpura nephritis, MCNS, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis | (antibodies) | [75] | |
GD3 | PAN nephropathy rat model | (kidney) | [26] |
O-acetylated-GD3 | Microalbuminuria associated with lead toxicity | (kidney) | [25] |
PAN nephropathy rat model | (kidney) | [26] | |
GM2 | INS (CMIP overexpression) | (podocytes) | [7] |
DN (glucosamine administration) | (mesangial cells) | [47] | |
GD2 | INS (CMIP overexpression) | (podocytes) | [7] |
GM1 | DN (glucosamine administration) | (mesangial cells) | [47] |
APOL1 associated FSGS | (podocyte rafts) | [8] | |
GD1α | APOL1 associated FSGS | (podocytes) | [8] |
APOL1 associated FSGS | (podocyte rafts) | [8] | |
GA1 | DN | Neg. correlation with eGFR | [48] |
APOL1 associated FSGS | (podocytes) | [8] |
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Savas, B.; Astarita, G.; Aureli, M.; Sahali, D.; Ollero, M. Gangliosides in Podocyte Biology and Disease. Int. J. Mol. Sci. 2020, 21, 9645. https://doi.org/10.3390/ijms21249645
Savas B, Astarita G, Aureli M, Sahali D, Ollero M. Gangliosides in Podocyte Biology and Disease. International Journal of Molecular Sciences. 2020; 21(24):9645. https://doi.org/10.3390/ijms21249645
Chicago/Turabian StyleSavas, Berkan, Giuseppe Astarita, Massimo Aureli, Dil Sahali, and Mario Ollero. 2020. "Gangliosides in Podocyte Biology and Disease" International Journal of Molecular Sciences 21, no. 24: 9645. https://doi.org/10.3390/ijms21249645