COLLAGEN, the major extracellular protein of most tissues, is considered a relatively inert macromolecule, with a turnover rate slower than that of most proteins1. There is, however, a portion of the total collagen pool that is rapidly turning over, for tracer studies of collagen metabolism in intact animals have demonstrated that a significant amount of newly synthesised collagen is apparently degraded within hours of its synthesis2. Further, direct evidence for the rapid degradation of collagen has been provided by studies of rabbit lung explants which showed that 30-40% of newly synthesised collagen was degraded within minutes of its synthesis3. This phenomenon is of interest because it involves such a large proportion of collagen production, and thus may significantly influence the quantity of collagen within a tissue and hence organ structure and function. The time course of this rapid degradation of collagen suggests that it occurs within the collagen-producing cells before its secretion. Although it has been repeatedly demonstrated that intracellular degradative processes have a central role in regulating the quantity of proteins that function within cells, intracellular degradation has not been considered a general mechanism for regulating the quantity of proteins destined for extracellular function4-6. We describe here a direct evaluation of the hypothesis that extracellular levels of collagen are regulated, in part, by the rapid degradation of newly synthesised collagen before it reaches the extracellular space. We have studied the size and kinetics of collagen production by fibroblasts in culture, and have found that not only is a significant proportion of newly synthesised collagen degraded intracellularly, but also that the process can be modulated by manipulating the structure of the collagen molecule.
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