New insights on glucosylated lipids: Metabolism and functions

Abstract

Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids.

Activation of iNKT cells by a distinct constituent of the endogenous glucosylceramide fraction

“…Mammalian serum contains a diversity of lipids, including GlcCers and other glycolipids (16)(17)(18). We next investigated the polar lipids from the sera of human, mouse, rat, rabbit, calf, goat, sheep, horse, pig, chicken, and fish.…”

Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity

“…The composition of β-GlcCer acyl chains (i.e., length and saturation) differs among tissues (18,36). C24:1 is abundantly expressed in brain tissue (36,37) and accumulates greatly in Gaucher disease patients (38).…”

“…One such ceramide is β-glucosylceramide (β-GlcCer), which is the first intermediate in the synthesis of a large family of GSLs. In healthy individuals, β-GlcCer is thought to be localized in the endoplasmic reticulum/Golgi apparatus (13)(14)(15), and the intracellular level of β-GlcCer is tightly regulated by a balance between biosynthesis and degradation to maintain tissue homeostasis (16)(17)(18). Therefore, an elevation in the levels of β-GlcCer in the extracellular milieu might signal massive cell death or tissue damage.…”

Phosphoregulation of the Ceramide Transport Protein CERT at Serine 315 in the Interaction with VAMP-associated Protein (VAP) for Inter-organelle Trafficking of Ceramide in Mammalian Cells

“…Lactosylceramide was from Nagara Science (Gifu, Japan). Ricinus communis lectin (RCA 120) was from Vector Laboratories Inc. N-[palmitoyl- [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]Palmitoyl-Derythro-sphingosine ([ 14 C]ceramide) (55 mCi/mmol) was from American Radiolabeled Chemicals. ISP-1/myriocin (16) was a gift from Dr. Tetsuro Fujita (Research Institute for Production Development, Japan).…”

“…Ceramide is newly synthesized in the endoplasmic reticulum (ER) 3 and is transported to the transGolgi region for its conversion to sphingomyelin (SM) (3)(4)(5). Ceramide is also converted to glucosylceramide at the cis-Golgi region and/or a subregion of the ER (6). Glucosylceramide is converted to more complex glycosphingolipids in the medial/ trans-Golgi regions (7,8).…”