Biosynthesis and Functions of Glycosphingolipid (GSL)

GSLs are widely found in the phospholipid bilayer of cell membranes. GSLs are amphiphilic molecules consisting of a variable carbohydrate-rich hydrophilic head group and a hydrophobic ceramide tail. Hundreds of glycans are attached to dozens of different ceramide molecules to produce structurally complex and diverse GSLs. GSLs are synthesized by enzymes localized in the endoplasmic reticulum and Golgi apparatus in a non-template-driven process, and internalized by endocytosis to form multivesicular bodies. Next, they are cleaved in the lysosomes. GSLs are not only cell membrane components necessary for cellular structural integrity, but also important bioactive compounds with various functions, such as affecting the sorting and transport of proteins, participating in cell adhesion and migration, growth and proliferation, signal transduction of internal and extracellular differentiation, and apoptosis.

Fig.1 Structure and synthesis of GSL. (Aerts, et al., 2019)

GSL-based Cell Surface Glycoengineering Service at CD BioGlyco

Since changes in GSL concentration and modification of molecular structure are involved in various diseases, studies of altered expression of GSLs may have relevant value for the discovery of disease-related biomarkers. Thus, understanding the exact molecular structure of GSLs and the pathways involved will further advance the therapeutic application of GSLs. We provide GSL modification and analysis services on cell surfaces.

• Modification service

Glycosylation is a fundamental modification of cell surface glycolipids. We modify the GSL-based cell surface by interfering with the glycosylation reactions involved in GSL biosynthesis and secretion pathways, primarily at the inner surface of Golgi and trans-Golgi network (TGN) membranes. Our researchers have extensive modification experience to provide accurate and rapid GSL-based cell surface modification services. Notably, a portion of the GSL is transported to the plasma membrane via cytosolic efflux membrane streams to be expressed in a cell-type specific pattern. Thus, we modify this portion of the GSL by metabolic reactions at or near the cell surface.

• Biosynthesis and metabolic analysis services

During epithelial-to-mesenchymal transition (EMT), modification of GSL expression at the cell surface alters the receptor tyrosine kinase (RTKs) downstream signaling pathways. CD BioGlyco provides reliable metabolic services for GSLs by analyzing different EMT characteristics such as proliferation, migration/invasion, and tumorigenesis, as well as how cellular signaling pathways convert quiescent and polarized epithelial cells into migrating and invasive epithelial cells.

• Comprehensive analytical approach services

For serum or tissue samples, CD BioGlyco offers GSLs extraction isolation and purification services using different extraction methods such as organic extraction methods and sonication. After the methylation reaction, the resulting sphingolipids are characterized by primary mass spectrometry (MS¹) and multistage mass spectrometry (MSⁿ) to determine the species and specific structure of each major neutral sphingolipid. Liquid chromatography-mass spectrometry (LC-MS) is provided for the methylated neutral sphingolipids to accurately and quickly analyze the samples and provide data reports to our clients.

Fig.2 Flowchart of GSLs analysis service. (CD BioGlyco)

Applications of GSL-based Cell Surface Glycoengineering

• GSLs mediate cell-cell interactions and regulate signal transduction pathways. Their abnormal biosynthesis and metabolism lead to the occurrence of diseases, which plays a crucial role in the occurrence of tumor chemotherapy resistance.
• By reducing the amount of GSLs in the adipose tissue of obese mice, it restored insulin sensitivity and reduced inflammation.
• The study of abnormal changes of glycan structure in GSLs finds glycosyltransferases with abnormal glycan expression and then finds cancer-related glycans, to provide ideas for the diagnosis and treatment of cancer.
• GSLs help to correct the abnormal parts of tumor cells by studying the abnormal changes in lipid metabolism in cancer.
• Modification of the cell-surface GSL partly controls the disease onset, such as Inflammation of the central nervous system and neurodegeneration.

CD BioGlyco has always adhered to the client-centric principle. Our professional technical support follows up the whole process to answer any questions you may have.If you would like to learn more about Cell Surface Glycoengineering, please do not hesitate to contact us.