Erythrocyte signal transduction pathways, their oxygenation dependence and functional significance

Erythrocytes play a key role in human and vertebrate metabolism. Tissue O-2 supply is regulated by both hemoglobin ( Hb)-O-2 affinity and erythrocyte rheology, a key determinant of tissue perfusion. Oxygenation-deoxygenation transitions of Hb may lead to reorganization of the cytoskeleton and signalling pathways activation/ deactivation in an O-2- dependent manner. Deoxygenated Hb binds to the cytoplasmic domain of the anion exchanger band 3, which is anchored to the cytoskeleton, and is considered a major mechanism underlying the oxygenation-dependence of several erythrocyte functions. This work discusses the multiple modes of Hb- cytoskeleton interactions. In addition, it reviews the effects of Mg2+, 2,3- diphosphoglycerate, NO, shear stress and Ca2+, all factors accompanying the oxygenation-deoxygenation cycle in circulating red cells. Due to the extensive literature on the subject, the data discussed here, pertain mainly to human erythrocytes whose O-2 affinity is modulated by 2,3- diphosphoglycerate, ectothermic vertebrate erythrocytes that use ATP, and to bird erythrocytes that use inositol pentaphosphate. Copyright (C) 2005 S. Karger AG, Basel.