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First published online March 23, 2005
doi: 10.1242/10.1242/jcs.01731

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Procollagen trafficking, processing and fibrillogenesis

Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK

View larger version (122K): [in a new window]   Fig. 1. Transmission electron microscopy of cultured embryonic tendon fibroblasts shows randomly orientated extracellular collagen fibrils. A: bar, 2 µm; B: bar, 1 µm.

View larger version (27K): [in a new window]   Fig. 2. Overview of the steps involved in the production of collagen fibrils by fibroblasts. Procollagen chains are synthesized in the endoplasmic reticulum (ER), are brought together by interactions between the C-propeptides and fold to form a rod-like triple-helical domain flanked by globular N- and C-propeptides. The large number of post-translational modifications that occur in the ER are not depicted. Removal of the N- and C-propeptides from fully folded procollagen only occurs after transport of procollagen across the Golgi stacks and results in collagen molecules that are then able to assemble into fibrils. Covalent crosslinks occur within and between triple-helical collagen molecules in fibrils.

View larger version (115K): [in a new window]   Fig. 3. The fibripositor secretory pathway. (A) Transmission electron microscopy of transverse sections through embryonic mouse tail tendon shows bundles of extracellular collagen fibrils between adjacent cells. One (a), two (b), three (c) or more (not shown) membrane-bounded collagen fibrils are also frequently observed within the cytoplasm. Membrane-bounded collagen fibrils are also observed in plasma membrane (PM) extensions called fibripositors (d). Bar, 500 nm. (B-D) Schematics showing longitudinal representations of collagen fibrils in (B) a Golgi-to-PM transport compartment (GPC+cf) and within both (C) closed and (D) open fibripositors. The topology of membrane-bounded collagen fibrils observed in cross-section and the PM was determined by serial-section 3D reconstruction. Selected potential planes of section are represented by dotted lines. (a-c) Cross-section through one (a), two (b) and three (c) fibrils located within the cytoplasm; (d) cross-section through a single fibril located within a fibripositor.

View larger version (23K): [in a new window]   Fig. 4. Schematic of the activation pathway for the procollagen N- and C-proteinases. This enzyme cascade is initiated by autocatalytic activation of furin or furin-like proprotein convertases in the trans-Golgi network and is responsible for the processing of procollagen to collagen by ADAMTS (N-proteinase) and tolloid (C-proteinase) family enzymes. Amino acid sequences cleaved by furin are shown between the pro- and catalytic domains of the enzymes. The signal sequence for secretory targeting is represented as a black rectangle. Abbreviations: ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; BMP-1, bone morphogenetic protein 1; CUB domains, so-called owing to their occurrence in complement components, a sea urchin protein and BMP-1; EGF, epidermal growth factor; mTLD, mammalian tolloid; P-domain, region required for processing activity; Pro, prodomain, removal of which is required for enzyme activation; TLL-1, tolloid like 1; TSP, thrombospondin.