Subcellular targeting of multiligand-binding protein gC1qR.
gC1q receptor, a protein originally described as the cell surface receptor for the globular heads of complement factor C1q, has been found to bind human H-kininogen with high affinity and specificity. Therefore, gC1qR has been considered candidate kininogen docking site on the surfaces of platelets, neutrophils and endothelial cells. Recent work demonstrating that gC1qR is an intracellular protein that is tightly associated with mitochondria rather than targeted to the cell surface has challenged this view. To further probe cellular trafficking routes of gC1qR, we overexpressed human gC1qR in a mammalian cell and monitored cell surface exposure of recombinant gC1qR by virtue of its capacity to bind labeled H-kininogen. Transient transfection of COS1 cells with the full-length cDNA of human gC1qR resulted in a high level of recombinant protein that matched the pool of endogenous gC1qR present in these tells. Overexpression of gC1qR did not significantly increase the number of H-kininogen binding sites exposed by the transfected cells thus denying the possibility that alternative routing of gC1qR to the surface of COS1 cells occurs at significant levels. Hence gC1qR has the capacity to tightly bind H-kininogen, but because gC1qR is routed to mitochondria it cannot fulfill the postulated functions as a cell docking site for kininogens and complement factors.
Dedio
J
J
Institute of Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg-University at Mainz, Germany.
Renné
T
T
Weisser
M
M
Müller-Esterl
W
W
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D019556:COS Cells; D002352:Carrier Proteins; D015922:Complement C1q / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors; D008024:Ligands; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011499:Protein Processing, Post-Translational; D011951:Receptors, Complement / Q000096:biosynthesis / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008024:Ligands; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q