RRC ID 69856
Author Tanaka T, Moriya K, Tsunenaga M, Yanagawa T, Morita H, Minowa T, Tagawa YI, Hanagata N, Inagaki Y, Ikoma T.
Title Visualized procollagen Iα1 demonstrates the intracellular processing of propeptides.
Journal Life Sci Alliance
Abstract The processing of type I procollagen is essential for fibril formation; however, the steps involved remain controversial. We constructed a live cell imaging system by inserting fluorescent proteins into type I pre-procollagen α1. Based on live imaging and immunostaining, the C-propeptide is intracellularly cleaved at the perinuclear region, including the endoplasmic reticulum, and subsequently accumulates at the upside of the cell. The N-propeptide is also intracellularly cleaved, but is transported with the repeating structure domain of collagen into the extracellular region. This system makes it possible to detect relative increases and decreases in collagen secretion in a high-throughput manner by assaying fluorescence in the culture medium, and revealed that the rate-limiting step for collagen secretion occurs after the synthesis of procollagen. In the present study, we identified a defect in procollagen processing in activated hepatic stellate cells, which secrete aberrant collagen fibrils. The results obtained demonstrated the intracellular processing of type I procollagen, and revealed a link between dysfunctional processing and diseases such as hepatic fibrosis.
Volume 5(5)
Published 2022-5-1
DOI 10.26508/lsa.202101060
PII 5/5/e202101060
PMID 35181633
PMC PMC8860094
MeSH Collagen* / metabolism Endoplasmic Reticulum / metabolism Procollagen* / metabolism
IF 2.622
Human and Animal Cells NIH3T3-3-4(RCB1862)
DNA material Genome Network Project Human cDNA IRAK047I05 (HGY018997)