SOLUBLE FORM OF COMPLEMENT C3B C4B RECEPTOR (CR-1) RESULTS FROM A PROTEOLYTIC CLEAVAGE IN THE C-TERMINAL REGION OF CR-1 TRANSMEMBRANE DOMAIN/

The complement C3b/C4b receptor (CR1) is an integral protein, anchored in the plasma membrane through a hydrophobic domain of 25 amino acids , but is also found in the plasma in soluble form (sCR1). A recombinan t, soluble form of CR1 has been demonstrated to reduce complement-depe ndent tissue injury in animal models of ischaemia/reperfusion. In view of the important pathophysiological relevance of sCR1, we have invest igated the mechanisms governing CR1 release by using various mutated a nd chimaeric receptors transiently expressed in COS cells, Pulse-chase experiments revealed that (1) sCR1 is produced by a proteolytic proce ss, (2) the cleavage site lies within the C-terminus of CR1 transmembr ane domain, (3) the proteolytic process involves a fully glycosylated CR1 form and (4) this process rakes place in late secretory vesicles o r at the plasma membrane.