The glycosynapse

Abstract

Physically distinguishable microdomains associated with various functional membrane proteins are one of the major current topics in cell biology. Glycosphingolipids present in such microdomains have been used as “markers;” however, the functional role of glycosyl epitopes in microdomains has received little attention. In this review, I have tried to summarize the evidence that glycosyl epitopes in microdomains mediate cell adhesion and signal transduction events that affect cellular phenotypes. Molecular assemblies that perform such functions are hereby termed “glycosynapse” in analogy to “immunological synapse,” the membrane assembly of immunocyte adhesion and signaling. Three types of glycosynapses are so far distinguishable: (i) Glycosphingolipids organized with cytoplasmic signal transducers and proteolipid tetraspanin with or without growth factor receptors; (ii) transmembrane mucin-type glycoproteins with clustered O-linked glycoepitopes for cell adhesion and associated signal transducers at lipid domain; and (iii) N-glycosylated transmembrane adhesion receptors complexed with tetraspanin and gangliosides, as typically seen with the integrin–tetraspanin–ganglioside complex. The possibility is discussed that glycosynapses give rise to a high degree of diversity and complexity of phenotypes

The fate and function of glycosphingolipid glucosylceramide

“…They appear to be concentrated in the plasma membrane and in membranes of the endocytotic recycling system (Van Genderen et al 1991), and are generally thought to be limited to the non-cytoplasmic leaflet of the lipid bilayer. The enormous range of head group structures and their occurrence on the cell surface already suggested that they function in specific recognition between cells and in subsequent signalling towards the cell interior (Hakomori 2002). A breakthrough in our understanding of the molecular mechanism behind this signalling came when it was realized that the ceramide lipid backbone provides these lipids with special physical properties.…”

Fragmentation studies of noncovalent sugar-sugar complexes by infrared atmospheric pressure MALDI

“…Furthermore, protein-carbohydrate interactions are known to vary in binding affinity due to differing linkages within the carbohydrate. It is clear that sugars themselves have crucial roles in determining specificity of binding, and it has been speculated that carbohydrates are involved in cellular interactions themselves, without the need for protein involvement [6,7]. The wide variety of adoptable structures allows carbohydrates to have a range of potential hydrogen bond interactions with other sugars.…”

“…Sugars have been demonstrated to be the key sites of interactions between a variety of glycosphingolipids (GSLs) [8]. The sugar portion of the GSL has been shown to orient in a fashion amenable to interactions with other sugars [6,8]. These interactions often lead to downstream signaling pathways, involved in a variety of functions crucial for immune function [9].…”

From glycobiology to systems glycobiology: International network with Japanese scientists through consortia

“…Other Japanese scientists working mostly in the USA are Sen-ichiro Hakamori and Kunihiko Suzuki. Hakomori (7,8) made great contributions to the field of glycobiology and trained over 200 Japanese glycobiologists, and Kunihiko Suzuki (9) also trained many scientists in the field of brain lipids and related genetic disorders. Space limitation necessitates our citing more about other distinguished Japanese biochemists such as Ikuo Yamashina (glycoproteins), Sakaru Suzuki (proteoglycans), Tokuji Ikenaka (glycoproteins), Shigeru Tsuiki (glycoproteins), Akira Makita (glycolipids) and the late Yasuo Inoue (glycoproteins).…”