Intracellular degradation of newly synthesized collagen.
This chapter reviews recent work on intracellular degradation of newly synthesized collagen, the most abundant protein in the mammalian body. Approximately 10-20% of collagen synthesized by human fibroblasts under normal culture conditions is broken down rather than secreted; this is referred to as the basal level of degradation. It is not known where basal degradation occurs, but indirect evidence suggests a compartment of the secretory pathway, perhaps the Golgi complex. Intracellular degradation is increased when cells are induced to synthesize structurally abnormal collagen, either by incubation in the presence of amino acid analogs or because of mutations in collagen genes. There is evidence that lysosomal proteases mediate degradation of structurally abnormal collagen, however, recent work indicates that I-cells, which are genetically deficient in several lysosomal enzymes, can also degrade abnormal collagen. Modulation of the level of intracellular degradation can effect a change in net collagen production independently of changes in the rate of synthesis. Intracellular degradation of newly synthesized collagen has been observed in vivo, but it is not clear whether decreasing degradation contributes to increasing collagen production in fibrosis. This chapter concludes by relating collagen degradation to the more general phenomenon of intracellular degradation of newly synthesized secretory proteins, and by indicating directions for future work.
Bienkowski
R S
RS
Pediatric Research Center, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
D000595:Amino Acid Sequence; D000818:Animals; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D003094:Collagen; D011392:Proline; D000242:Cyclic AMP