Complement C1q inhibits cellular spreading and stimulates adenylyl cyclase activity of fibroblasts.
C1q selectively localizes at injured tissues, where it may function as a regulator of cell-matrix interactions. We show here that purified C1q, added to the culture medium of human gingival fibroblasts (HF) spread onto fibronectin substrates, elicited a round morphology that was accompanied by altered F-actin and correlated with inhibition of cellular spreading. Shape modification required integrity of the molecule and was specific, dose dependent, nontoxic, and reversible. Antispreading activity was mediated, at least in part, by specific cell-surface C1q receptors. We hypothesized that ligand occupancy of C1q receptors could influence shape by affecting intracellular levels of cyclic AMP (cAMP). Within 20 min of exposure of adhering HF to C1q, we detected an increase in adenylyl cyclase activity (six- to ninefold) in cAMP accumulation (by 20%) and in cAMP-dependent protein kinase activity (by 20%). These changes suggested that the rounding effect of C1q may be associated with activation of the adenylyl cyclase pathway.
Tan
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Department of Periodontics, University of Washington, Seattle 98195, USA.
Wong
S T
ST
Ghebrehiwet
B
B
Storm
D R
DR
Bordin
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002352:Carrier Proteins; D002478:Cells, Cultured; D015922:Complement C1q / Q000494:pharmacology* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D005353:Fibronectins / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement / Q000378:metabolism
C087299:C1QBP protein, human; D002352:Carrier Proteins; D005353:Fibronectins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q; D000242:Cyclic AMP; D000262:Adenylyl Cyclases