Stepwise proteolytic activation of type I procollagen to collagen within the secretory pathway of tendon fibroblasts in situ
| Autor: | EG Canty-Laird, Yinhui Lu, Karl E. Kadler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
mTLD
mammalian tolloid trans-Golgi network (TGN) Chick Embryo BFA brefeldin A pNcollagen procollagen lacking the C-propeptides but retaining the N-propeptides Biochemistry Amino Acid Chloromethyl Ketones Bone Morphogenetic Protein 1 Extracellular matrix Tendons chemistry.chemical_compound Mice 0302 clinical medicine ADAMTS a disintegrin and metalloprotease with thrombospondin motifs TGFβ transforming growth factor β Furin 0303 health sciences Secretory Pathway biology Procollagen N-Endopeptidase Brefeldin A Cell biology Dec-RVKR-CMK decanoyl-Arg-Val-Lys-Arg-chloromethylketone endoplasmic reticulum collagen collagen intermediate (a collective term for all procollagen pCcollagen pNcollagen and collagen molecules) Collagen furin Research Article trans-Golgi Network macromolecular substances C-proteinase Bone morphogenetic protein 1 Collagen Type I COPI coatomer protein 1 ER endoplasmic reticulum 03 medical and health sciences BMP1 bone morphogenetic protein 1 TLL tolloid-like Animals TEM transmission electron microscopy Molecular Biology Secretory pathway 030304 developmental biology PBS-T PBS with 0.1% Tween E embryonic day electron microscopy NP40 Nonidet P40 Endoplasmic reticulum pCcollagen procollagen lacking the N-propeptides but retaining the C-propeptides TGN trans-Golgi network Cell Biology MT1-MMP membrane type 1 matrix metalloproteinase Fibroblasts ERGIC ER–Golgi intermediate compartment Rats Enzyme Activation Procollagen peptidase chemistry N-proteinase biology.protein 030217 neurology & neurosurgery QL quantum level |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|