101. Soluble form of complement C3b/C4b receptor (CR1) results from a proteolytic cleavage in the C-terminal region of CR1 transmembrane domain.
- Author
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Hamer I, Paccaud JP, Belin D, Maeder C, and Carpentier JL
- Subjects
- Amino Acid Sequence, Animals, Brefeldin A, COS Cells, Cell Membrane metabolism, Cyclopentanes pharmacology, Electrophoresis, Polyacrylamide Gel, Endoplasmic Reticulum metabolism, Glycosylation, Humans, Lysosomes metabolism, Molecular Sequence Data, Mutagenesis, Precipitin Tests, Protein Processing, Post-Translational, Receptors, Complement 3b blood, Receptors, Complement 3b genetics, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins metabolism, Solubility, Urokinase-Type Plasminogen Activator genetics, Endopeptidases metabolism, Receptors, Complement 3b chemistry, Receptors, Complement 3b metabolism
- Abstract
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.
- Published
- 1998
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