Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ

Proteolytic cleavage of procollagen I to collagen I is essential for the formation of collagen fibrils in the extracellular matrix of vertebrate tissues. Procollagen is cleaved by the procollagen N- and C-proteinases, which remove the respective N- and C-propeptides from procollagen. Procollagen pro...

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Main Authors:	Canty-Laird, Elizabeth G., Lu, Yinhui, Kadler, Karl E.
Format:	Online
Language:	English
Published:	Portland Press Ltd. 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430002/

id	pubmed-3430002
recordtype	oai_dc
spelling	pubmed-34300022012-09-10 Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ Canty-Laird, Elizabeth G. Lu, Yinhui Kadler, Karl E. Research Article Proteolytic cleavage of procollagen I to collagen I is essential for the formation of collagen fibrils in the extracellular matrix of vertebrate tissues. Procollagen is cleaved by the procollagen N- and C-proteinases, which remove the respective N- and C-propeptides from procollagen. Procollagen processing is initiated within the secretory pathway in tendon fibroblasts, which are adept in assembling an ordered extracellular matrix of collagen fibrils in vivo. It was thought that intracellular processing was restricted to the TGN (trans-Golgi network). In the present study, brefeldin A treatment of tendon explant cultures showed that N-proteinase activity is present in the resulting fused ER (endoplasmic reticulum)–Golgi compartment, but that C-proteinase activity is restricted to the TGN in embryonic chick tendon fibroblasts. In late embryonic and postnatal rat tail and postnatal mouse tail tendon, C-proteinase activity was detected in TGN and pre-TGN compartments. Preventing activation of the procollagen N- and C-proteinases with the furin inhibitor Dec-RVKR-CMK (decanoyl-Arg-Val-Lys-Arg-chloromethylketone) indicated that only a fraction of intracellular procollagen cleavage was mediated by newly activated proteinases. In conclusion, the N-propeptides are removed earlier in the secretory pathway than the C-propeptides. The removal of the C-propeptides in post-Golgi compartments most probably indicates preparation of collagen molecules for fibril formation at the cell–matrix interface. Portland Press Ltd. 2011-12-21 2012-01-15 /pmc/articles/PMC3430002/ /pubmed/21967573 http://dx.doi.org/10.1042/BJ20111379 Text en © 2012 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Canty-Laird, Elizabeth G. Lu, Yinhui Kadler, Karl E.
spellingShingle	Canty-Laird, Elizabeth G. Lu, Yinhui Kadler, Karl E. Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
author_facet	Canty-Laird, Elizabeth G. Lu, Yinhui Kadler, Karl E.
author_sort	Canty-Laird, Elizabeth G.
title	Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
title_short	Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
title_full	Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
title_fullStr	Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
title_full_unstemmed	Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
title_sort	stepwise proteolytic activation of type i procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
description	Proteolytic cleavage of procollagen I to collagen I is essential for the formation of collagen fibrils in the extracellular matrix of vertebrate tissues. Procollagen is cleaved by the procollagen N- and C-proteinases, which remove the respective N- and C-propeptides from procollagen. Procollagen processing is initiated within the secretory pathway in tendon fibroblasts, which are adept in assembling an ordered extracellular matrix of collagen fibrils in vivo. It was thought that intracellular processing was restricted to the TGN (trans-Golgi network). In the present study, brefeldin A treatment of tendon explant cultures showed that N-proteinase activity is present in the resulting fused ER (endoplasmic reticulum)–Golgi compartment, but that C-proteinase activity is restricted to the TGN in embryonic chick tendon fibroblasts. In late embryonic and postnatal rat tail and postnatal mouse tail tendon, C-proteinase activity was detected in TGN and pre-TGN compartments. Preventing activation of the procollagen N- and C-proteinases with the furin inhibitor Dec-RVKR-CMK (decanoyl-Arg-Val-Lys-Arg-chloromethylketone) indicated that only a fraction of intracellular procollagen cleavage was mediated by newly activated proteinases. In conclusion, the N-propeptides are removed earlier in the secretory pathway than the C-propeptides. The removal of the C-propeptides in post-Golgi compartments most probably indicates preparation of collagen molecules for fibril formation at the cell–matrix interface.
publisher	Portland Press Ltd.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430002/
_version_	1611552926007820288

Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ

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