Soluble form of complement C3b/C4b receptor (CR1) results from a proteolytic cleavage in the C-terminal region of CR1 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 recombinant, soluble form of CR1 has been demonstrated to reduce complement-dependent tissue injury in animal models of ischaemia/reperfusion. In view of the important pathophysiological relevance of sCR1, we have investigated the mechanisms governing CR1 release by using various mutated and chimaeric receptors transiently expressed in COS cells. Pulse-chase experiments revealed that (1) sCR1 is produced by a proteolytic process, (2) the cleavage site lies within the C-terminus of CR1 transmembrane domain, (3) the proteolytic process involves a fully glycosylated CR1 form and (4) this process takes place in late secretory vesicles or at the plasma membrane.
Hamer
I
I
Department of Morphology Department of Pathology, University of Geneva, CMU, Rue Michel Servet, 1, CH-1211 Geneva 4, Switzerland.
Paccaud
J P
JP
Belin
D
D
Maeder
C
C
Carpentier
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D020126:Brefeldin A; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D017463:Receptors, Complement 3b / Q000097:blood / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
D003517:Cyclopentanes; D017463:Receptors, Complement 3b; D011993:Recombinant Fusion Proteins; D020126:Brefeldin A; D010450:Endopeptidases; D014568:Urokinase-Type Plasminogen Activator