Membrane microdomains or
lipid/membrane rafts are distinct areas on the plasma membranes, where a specific subset of
lipids (e.g.
cholesterol,
sphingolipids) and
proteins (e.g.
glycosylphosphatidylinositol-anchored
proteins,
growth factor receptor/
kinases) are getting together and functioning for several aspects of cellular functions. Our recent investigation has revealed that fertilization of African clawed frog, Xenopus laevis, requires
cholesterol-dependent nature of egg membrane microdomains. Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic
tyrosine residue of
uroplakin III, an egg membrane microdomain-associated
protein.
Protease activity toward
uroplakin III seems to be derived from fertilizing sperm, while phosphorylation of
uroplakin III seems to be catalyzed by the egg
tyrosine kinase Src, whose activation is required for cytoplasmic rearrangement of fertilized eggs; so-called 'egg activation'. Therefore, it is assumed that
uroplakin III serves an integral part of signal transduction in fertilization of Xenopus. Our more recent study on human
cancer cells has revealed that a similar but distinct scheme of signal transduction operates in anti-apoptotic growth of cells. Namely, in human bladder
carcinoma cells, cooperation of
uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum. In this review, I briefly introduce about biology of fertilization and
cancer, and then present and discuss our experimental data on general importance and specific features of membrane microdomains in Xenopus fertilization and anti-apoptosis in human bladder
carcinoma cells.