Structure and function of glycosphingolipids and sphingolipids: Recollections and future trends

• Published in: Biochimica et biophysica acta Vol. 1780; no. 3; pp. 325 - 346
• Main Author: Hakomori, Sen-itiroh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2008
• Subjects: Animals; Carbohydrate–carbohydrate interaction; Cell Adhesion; Cell growth; Cell motility; Cell Transformation, Neoplastic; Contact inhibition; Developmentally regulated antigen; Epigenetic regulation; Epithelial–mesenchymal transition (EMT); Epitopes; Ganglio-series; Globo-series; Glycosphingolipid; Glycosphingolipids - chemistry; Glycosphingolipids - metabolism; Glycosyl epitope; Glycosynapse; Growth factor receptor; Humans; Integrin; Lacto-series; Membrane Microdomains - metabolism; Microdomain; Niche; Protein kinase Cδ; Signal Transduction; Sphingosine-dependent kinase; Stem cell; Tetraspanin; Tumor-associated antigen; Contact inhibition; Glycosyl epitope; LN; Microdomain; Developmentally regulated antigen; Stem cell; FN; Sph; Globo-series; Epigenetic regulation; EGFR; Sphingosine-dependent kinase; Signal transduction; Cell growth; Integrin; Glycosphingolipid; Tumor-associated antigen; Cell adhesion; PDGFR; Niche; Csk; SSEA; Carbohydrate–carbohydrate interaction; Sph-1-P; GSL; Epithelial–mesenchymal transition (EMT); FGF; EGF; MS; CCI; PKC; Glycosphingolipids are abbreviated as recommended by the IUPAC-IUB Commission on Biochemical Nomenclature ( Biochem J 171: 21–35, 1978, Table I) however, the suffix -Ose or -OseCer is omitted. Ganglio-series gangliosides are abbreviated according to the extended version of Svennerholm's list (e.g., Holmgren et al., Proc Natl Acad Sci USA 77: 1947–1950, 1980); DMS; Protein kinase Cδ; EMT; FGFR; GEM; Ganglio-series; TSP; Lacto-series; Cell motility; Growth factor receptor; PDGF; Glycosynapse; TMS; Tetraspanin
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2007.08.015

Based on development of various methodologies for isolation and characterization of glycosphingolipids (GSLs), we have identified a number of GSLs with globo-series or lacto-series structure. Many of them are tumor-associated or developmentally regulated antigens. The major question arose, what are their functions in cells and tissues? Various approaches to answer this question were undertaken. While the method is different for each approach, we have continuously studied GSL or glycosyl epitope interaction with functional membrane components, which include tetraspanins, growth factor receptors, integrins, and signal transducer molecules. Often, GSLs were found to interact with other carbohydrates within a specific membrane microdomain termed “glycosynapse”, which mediates cell adhesion with concurrent signal transduction. Future trends in GSL and glycosyl epitope research are considered, including stem cell biology and epithelial–mesenchymal transition (EMT) process.