Signal transduction in leucocytes via GPI-anchored proteins: an experimental artefact or an aspect of immunoreceptor function?

Membrane proteins anchored in the membrane via a glycolipid glycosylphosphatidylinositol (GPI) as well as some glycolipids are able to transduce signals and induce diverse functional responses in cells upon their cross-linking via antibodies or natural ligands. In some cases this signaling capacity seems to be due to associations of these molecules with specific transmembrane proteins. GPI-anchored proteins are components of membrane microdomains enriched in glycosphingolipids and cholesterol and devoid of most transmembrane proteins. These membrane specializations are relatively resistant to solubilization in solutions of some mild detergents at low temperatures. These 'GPI-microdomains' contain also cytoplasmic signaling molecules such as Src-family protein tyrosine kinases and trimeric G-proteins. Thus, at least some signaling elicited upon cross-linking of GPI-anchored proteins and glycolipids may be due to perturbation of the signaling molecules associated with these microdomains. It is suggested that these specialized areas of the membrane rich in signaling molecules interact with immunoreceptors (TCR, BCR, Fc receptors) cross-linked upon their interactions with ligands and importantly contribute to initiation of proximal phases of their signaling pathways.