Carbohydrate-to-carbohydrate interaction, through glycosynapse, as a basis of cell recognition and membrane organization

Cell adhesion mediated by carbohydrate-to-carbohydrate interaction (CCI), or cell adhesion with concurrent signal transduction, are discussed in three contexts. 1. Types of cell adhesion based on interaction of several combinations of glycosphingolipids (GSLs) at the surface of interfacing cells (trans interaction) are reviewed critically, to exclude the possible involvement of GSL-binding proteins. Special emphasis is on: (i) autoaggregation of mouse teratocarcinoma F9 cells mediated by Lex-to-Lex interaction, in which presence of Lex-binding protein is ruled out; (ii) adhesion of GM3-expressing cells to Gg3-expressing cells, in which involvement of GM3- or Gg3-binding protein is ruled out. 2. Characteristic features and requirements of CCI, as compared with carbohydrate-to-protein interaction (CPI) and protein-to-protein interaction (PPI), are summarized, including: (i) specificity and requirement of bivalent cation; (ii) reaction velocity of CCI as compared to PPI; (iii) negative (repulsive) interaction; (iv) synergistic or cooperative effect of CCI and PPI, particularly GM3-to-Gg3 or GM3-to-LacCer interaction in synergy with integrin-dependent adhesion, or Lex-to-Lex interaction in cooperation with E-cadherin-dependent adhesion. 3. Microdomains at the cell surface are formed based on clustering of GSLs or glycoproteins organized with signal transducers. Among such microdomains, those involved in adhesion coupled with signal transduction to alter cellular phenotype are termed glycosynapse. In some glycosynapses, growth factor receptors or integrin receptors are also involved, and their function is modulated by GSLs only when the receptor is N-glycosylated. This modulation may occur in part via interaction of GSLs with N-linked glycans of the receptor, termed cis interaction.