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.
Highlights
AND HISTORICAL RETROSPECTIVEThe concept of microdomains in plasma membrane evolved from questions about the original ‘‘fluid mosaic’’ model of Singer and Nicolson (1972), in which membrane proteins are randomly distributed in the ‘‘sea’’ of homogeneous lipid bilayer
We found recently that MUC1 and other mucin-type glycoproteins, together with Src family kinases, are expressed in low-density
We found unexpectedly that three mucin-type glycoproteins, MUC1, P-selectin glycoprotein ligand-1 (PSGL-1), and CD45, are all resistant to 1% Brij 48 or 500 mM Na2CO3, and all present in low-density membrane fraction, associated with Src kinases (Handa et al 2001)
Summary
The concept of microdomains in plasma membrane evolved from questions about the original ‘‘fluid mosaic’’ model of Singer and Nicolson (1972), in which membrane proteins are randomly distributed in the ‘‘sea’’ of homogeneous lipid bilayer. H.B. White (Jain and White 1977), which emphasized that the ‘‘biomembrane continuum is broken up into a number of relative rigid plates or patches which are in relative motion with respect to each other’’ may be the first alternative to the Singer and Nicolson model, addressing the above questions. White (Jain and White 1977), which emphasized that the ‘‘biomembrane continuum is broken up into a number of relative rigid plates or patches which are in relative motion with respect to each other’’ may be the first alternative to the Singer and Nicolson model, addressing the above questions According to this model, the ordered and rigid regions are separated from each other by fluid and disordered regions. The concept of microdomains mediating cell adhesion, carbohydrate-dependent adhesion coupled with signaling, was developed only recently, and was termed ‘‘glycosynapse’’ (see below) (Iwabuchi et al 1998a, b, Hakomori et al 1998, Hakomori 2000)
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