Formation of gamma-glutamyl-epsilon-lysine bridges between membrane proteins by a Ca2+-regulated enzyme in intact erythrocytes.
A rise in the intracellular concentration of Ca2+-ions in human erythrocytes causes the formation of high-molecular-weight membrane protein polymers, cross-linked by gamma-glutamyl-epsilon-lysine side chain bridges. Cross-linking involves proteins at the cytoplasmic side of the membrane (band 4.1, spectrin, and band 3 materials) and the reaction is catalyzed by the intrinsic transglutaminase. This enzyme is regulated by Ca2+-ions and it exits in a latent form in normal cells. The protein polymer, isolated from the membranes of Ca2+-loaded intact human red cells, is heterogeneous in size and may contain as many as 6 moles of gamma-glutamyl-epsilon-lysine cross-links per 100,000 gm of protein. Synthetic compounds, which either compete against the epsilon-lysine cross-linking functionalities of the protein substrates (eg, histamine, aminoacetonitrile, cystamine) or directly inactivate the transamidase (eg, cystamine), inhibit the membrane polymerization reaction in intact human erythrocytes. They also interfere with the Ca2+-induced irreversible shape change from discocyte to echinocyte and inhibit the irreversible loss of membrane deformability. Thus, the transamidase-catalyzed production of gamma-glutamyl-epsilon-lysine cross-links in the membrane may be a common denominator in these cellular manifestations.
D002118:Calcium / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D004913:Erythrocytes, Abnormal / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000097:blood*
D005971:Glutamates; D008565:Membrane Proteins; D005723:gamma-Glutamyltransferase; D008239:Lysine; D002118:Calcium