everal leukocyte surface proteins are anchored in the membrane via the glycolipid glycosylphosphatidylinositol (GPI) 1 (Fig. 1). A striking feature of these structurally diverse proteins (see Box 1) is that their ligation on the cell surface by suitable antibodies results in signal transduction that is characterized by: (1) transient elevation of cytoplasmic [Ca 2ϩ ]; (2) tyrosine phosphorylation of cellular substrates; (3) initiation of effector functions such as oxidative burst or degranulation in granulocytes; and (4) even triggering of T-cell proliferation and functional differentiation into effector cells 2,3 . Such signalling capacity is surprising considering that these molecules have no transmembrane and intracellular moieties and thus no direct contact with the cell interior. Similarly, crosslinking of some glycolipids by antibodies also elicits signal transduction and cellular responses 4,5 .
GPI-complexes and membrane microdomains
Another characteristic feature of the GPI-anchored proteins is that, following membrane solubilization by most types of mild detergents at low temperature, they are found in large detergent-insoluble complexes enriched in GPI-anchored proteins, glycosphingolipids, cholesterol, Src family protein tyrosinekinases (PTKs) and G-proteins but devoid of most transmembrane proteins 6-10 . These 'GPIcomplexes' [also called glycosphingolipidcholesterol rafts, detergent-insoluble glycolipid-enriched domains (DIGs) 11 or glycosphingolipid-enriched membrane domains (GEMs) 12 ] are of low buoyant density under the conditions of density gradient ultracentrifugation. The detergent-resistant GPI-complexes seem to correspond to membrane microdomains of distinct composition, different from the rest of the membrane. The GPI-microdomains can be viewed, with some simplification, as small semi-liquid islands floating in the more liquid phospholipid-rich bulk of the leukocyte membrane (Fig. 2). Structures similar to leukocyte GPI-microdomains seem to exist in many, perhaps most, cell types and have been thoroughly studied especially in polarized epithelial and endothelial cells (reviewed in Ref. 11). In these cells, the GPI-microdomains (rafts, DIGs) can fuse to form much larger membrane sheets and comprise a considerable part of the apical surface of these cells although being largely absent