Expression of ceramide glucosyltransferases, which are essential for glycosphingolipid synthesis, is only required in a small subset ofC. eleganscells

Abstract

Glycosphingolipids (GSLs) are glycosylated derivatives of ceramide in the lipid bilayer. Their ubiquitous distribution and complexity suggest that they have important functions, but what these are in vivo is still poorly understood. Here, we characterize the phenotype of Caenorhabditis elegans mutants with essentially no GSLs. The C. elegans genome encodes three ceramide glucosyltransferase (CGT) genes, which encode enzymes required for GSL biosynthesis. Animals lacking CGT do not synthesize GSLs, arrest growth at the first larval stage, and display defects in a subset of cells in their digestive tract; these defects impair larval feeding, resulting in a starvation-induced growth arrest. Restoring CGT function in these digestive tract cells – but not in a variety of other tissues – is sufficient to rescue the phenotypes associated with loss of CGT function. These unexpected findings suggest that GSLs are dispensable in most C. elegans cells, including those of the nervous system.

A Caenorhabditis elegans Glycolipid-binding Galectin Functions in Host Defense against Bacterial Infection

“…Recently, it has been reported that ceramide glucosyltransferase genes involved in the biosynthesis of glycosphingolipids are strongly expressed in the pharyngeal-intestinal valve and in a small group of cells in the tail (37), similar to LEC-8::EGFP expression. It is also of interest how LEC-8 might function cooperatively with glycosphingolipids in those cells in C. elegans.…”

Caenorhabditis elegans as a model to study sphingolipid signaling

“…Dashes indicate no phenotype reported. 1 (Liu et al, 2014); 2 (Menuz et al, 2009); 3 (Deng et al, 2008); 4 ; 5 ; 6 (Mendel et al, 2003); 7 (Lin et al, 1998); 8 (Gulbins et al, 2013); 9 (Kim and Sun, 2012); 10 (Marza et al, 2009); 11 (Zhang et al, 2011).…”

“…In contrast to mammals and flies, which synthesize a single CGT protein, the C. elegans genome encodes three CGT proteins: CGT-1, CGT-2 and CGT-3 (Ichikawa and Hirabayashi, 1998;Leipelt et al, 2001). All CGTs generate glucosylceramide (GlcCer), the precursor of all C. elegans GSLs with CGT-3 possessing the highest enzymatic activity (Leipelt et al, 2001;Marza et al, 2009;Nomura et al, 2011). Double knock-down of cgt-1;cgt-2 by RNAi reduced overall enzymatic activity by 40%, whereas cgt-1;cgt-3 or cgt-2;cgt-3 double RNAi knock-down reduced enzymatic activity by 86% each (Nomura et al, 2011).…”

New insights on glucosylated lipids: Metabolism and functions

“…Knockout and/or knockdown of UGCG are lethal in mouse, Drosophila, and C. elegans, indicating a crucial role for GlcCer and GSLs synthesized from GlcCer during embryogenesis [35,36,52,53]. Ugcg knockout mice die in utero, because gastrulation is blocked by ectodermal apoptosis [53,54].…”

“…Three UGCG genes exist in C. elegans. Knockdown of all three UGCG genes causes growth arrest at the first larval stage [52]. It was recently identified using a global C. elegans tubulogenesis screening assay that UGCG is a critical enzyme for epithelial polarity [56].…”