Glycosynapses: microdomains controlling carbohydrate-dependent cell adhesion and signaling

Abstract

The concept of microdomains in plasma membranes was developed over two decades, following observation of polarity of membrane based on clustering of specific membrane components. Microdomains involved in carbohydrate-dependent cell adhesion with concurrent signal transduction that affect cellular phenotype are termed "glycosynapse". Three types of glycosynapse have been distinguished: "type 1" having glycosphingolipid associated with signal transducers (small G-proteins, cSrc, Src family kinases) and proteolipids; "type 2" having O-linked mucin-type glycoprotein associated with Src family kinases; and "type 3" having N-linked integrin receptor complexed with tetraspanin and ganglioside. Different cell types are characterized by presence of specific types of glycosynapse or their combinations, whose adhesion induces signal transduction to either facilitate or inhibit signaling. E.g., signaling through type 3 glycosynapse inhibits cell motility and differentiation. Glycosynapses are distinct from classically-known microdomains termed "caveolae", "caveolar membrane", or more recently "lipid raft", which are not involved in carbohydrate-dependent cell adhesion. Type 1 and type 3 glycosynapses are resistant to cholesterol-binding reagents, whereas structure and function of "caveolar membrane" or "lipid raft" are disrupted by these reagents. Various data indicate a functional role of glycosynapses during differentiation, development, and oncogenic transformation.

Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway

“…The next day, the mixture GSL/nanosphere was dried and resuspended in serum-free RPMI medium 1640 to a final volume of 1 ml by sonicating 10 min. The molar ratio of ganglioside/nanosphere binding was determined by using 3 Determination of Cell Motility, Its Inhibition by GSL-Nanospheres, and the Effect of mAb 8E11 That Blocks Motility-Inhibitory Effect of GSL-Nanospheres. Cell motility was determined as the area of phagokinetic tracks on gold sol particle-coated plates, as described in ref.…”

Regulation of the Transport and Protein Levels of the Inositol Phosphorylceramide Mannosyltransferases Csg1 and Csh1 by the Ca2+-binding Protein Csg2

“…2 are ubiquitous and abundant components of the eukaryotic plasma membrane that function in numerous cellular processes, such as proliferation, differentiation, and adhesion (1). They are also involved in the formation of membrane lipid microdomains (lipid rafts), which serve as platforms for effective signal transduction (2).…”

Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase

“…Gangliosides are sialic acid-containing glycosphingolipids that are enriched in glycolipid-enriched microdomain (GEM) 2 / rafts on the plasma membrane of cells (1,2). Normal adult brain tissues express gangliosides GM1, GD1a, GD1b, and GT1b as major components and express minimal levels of GD3 and GD2 (3,4).…”