Glycosphingolipids (GSLs) and sphingomyelin in animal cells are clustered a
nd organized as membrane microdomains closely associated with various signa
l transducer molecules such as cSrc, Src family kinases, small G-proteins (
e.g., RhoA, Ras), and focal adhesion kinase. GSL clustering in such microdo
mains causes adhesion to complementary GSLs on the surface of counterpart c
ells or presented on plastic surfaces, through carbohydrate-to-carbohydrate
interaction. GEL-dependent cell adhesion In microdomain causes activation
of the signal transducers, leading to cell phenotypic changes. A retrospect
ive of the development of this concept, and current status of our studies,
are presented.