Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development

Townley, Anna K.; Feng, Yi; Schmidt, Katy; Carter, Deborah A.; Porter, Robert P.; Verkade, Paul; Stephens, David

doi:10.1242/jcs.031070

Cited by 155 publications

(178 citation statements)

References 40 publications

(55 reference statements)

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“…This may be exemplified by a previous study showing that suppression of COPII components Sec13/31 causes defective type I collagen trafficking at the ER exit site, whereas transport of smaller cargos is unperturbed (40). Although p180 is able to enhance pleiomorphic carrier formation at the TGN, our previous report also confirmed that p180-depleted cells retained the normal secretory function for procollagen transport out of the ER (21), consistent with our present finding that low, but distinct, levels of collagens were secreted by p180-depleted cells.…”

Section: Discussionmentioning

confidence: 81%

Enhancement of Procollagen Biosynthesis by p180 through Augmented Ribosome Association on the Endoplasmic Reticulum in Response to Stimulated Secretion

Ueno

Tanaka

Kaneko

et al. 2010

Journal of Biological Chemistry

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A coiled-coil microtubule-bundling protein, p180, was originally reported as a ribosome-binding protein on the rough endoplasmic reticulum (ER) and is highly expressed in secretory tissues. Recently, we reported a novel role for p180 in the transGolgi network (TGN) expansion following stimulated collagen secretion. Here, we show that p180 plays a key role in procollagen biosynthesis and secretion in diploid fibroblasts. Depletion of p180 caused marked reductions of secreted collagens without significant loss of the ER membrane or mRNA. Metabolic labeling experiments revealed that the procollagen biosynthetic activity was markedly affected following p180 depletion. Moreover, loss of p180 perturbs ascorbate-stimulated de novo biosynthesis mainly in the membrane fraction with a preferential secretion defect of large proteins. At the EM level, one of the most prominent morphological features of p180-depleted cells was insufficient ribosome association on the ER membranes. In contrast, the ER of control cells was studded with numerous ribosomes, which were further enhanced by ascorbate. Similarly biochemical analysis confirmed that levels of membrane-bound ribosomes were altered in a p180-dependent manner. Taken together, our data suggest that p180 plays crucial roles in enhancing collagen biosynthesis at the entry site of the secretory compartments by a novel mechanism that mainly involves facilitating ribosome association on the ER. Entry of proteins into the secretory pathway via the rough endoplasmic reticulum (ER)3 is essential for intracellular transport of proteins to secretory compartments within the cell and finally to the extracellular milieu. In tissues with high secretory activity, such as the pancreas, the secretory apparatus is highly developed. One of the morphological hallmarks in such tissues is drastic proliferation of rough ER membranes that are densely occupied by ribosomes, whereas the rough ER in other tissues forms a loose network of tubular cisternae sparsely studded with ribosomes (1). However, the molecular basis for the biogenesis and proliferation of the rough ER in secretory tissues is largely unknown (1, 2).Collagen is one of the major components of the extracellular matrix (ECM) in connective tissues such as skin, tendon, and bone. It is synthesized on the ER membrane as a precursor form, i.e. procollagen, and secreted by professional secretory cells including fibroblasts. Fully consistent with the normal secretory pathway, procollagen is cotranslationally translocated into the lumen of the ER. Much interest has been focused on the mechanisms of its folding and trimerization processes in the ER, such as the hydroxylation enzymes for proline and lysine residues (reviewed in Refs. 3 and 4)). Recently, there has been considerable interest in the intracellular trafficking mechanism of procollagen as a representative model for supramolecular cargos (5-7). In addition, the regulation of procollagen biosynthesis has been intensively studied at the transcriptional level (8, 9) as well as at the...

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Section: Discussionmentioning

confidence: 81%

Enhancement of Procollagen Biosynthesis by p180 through Augmented Ribosome Association on the Endoplasmic Reticulum in Response to Stimulated Secretion

Ueno

Tanaka

Kaneko

et al. 2010

Journal of Biological Chemistry

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“…An example is SEC23A (Saccharomyces cerevisiae; Sec23a), known to be required for normal collagen production and secretion (Townley et al 2008) and important for craniofacial development (Lang et al 2006). Transillumination of the chest wall in the LacZstained Sec23a mutant revealed a pattern of muscle, vasculature, and cartilage staining (Fig.…”

Section: Connective Tissue and Cartilagementioning

confidence: 99%

A lacZ reporter gene expression atlas for 313 adult KOMP mutant mouse lines

et al. 2015

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Expression of the bacterial beta-galactosidase reporter gene (lacZ) in the vector used for the Knockout Mouse Project (KOMP) is driven by the endogenous promoter of the target gene. In tissues from KOMP mice, histochemical staining for LacZ enzyme activity can be used to determine gene expression patterns. With this technique, we have produced a comprehensive resource of gene expression using both whole mount (WM) and frozen section (FS) LacZ staining in 313 unique KOMP mutant mouse lines. Of these, ∼80% of mutants showed specific staining in one or more tissues, while ∼20% showed no specific staining, ∼13% had staining in only one tissue, and ∼25% had staining in >6 tissues. The highest frequency of specific staining occurred in the brain (∼50%), male gonads (42%), and kidney (39%). The WM method was useful for rapidly identifying whole organ and some substructure staining, while the FS method often revealed substructure and cellular staining specificity. Both staining methods had >90% repeatability in biological replicates. Nonspecific LacZ staining occurs in some tissues due to the presence of bacteria or endogenous enzyme activity. However, this can be effectively distinguished from reporter gene activity by the combination of the WM and FS methods. After careful annotation, LacZ staining patterns in a high percentage of mutants revealed a unique structure-function not previously reported for many of these genes. The validation of methods for LacZ staining, annotation, and expression analysis reported here provides unique insights into the function of genes for which little is currently known.[Supplemental material is available for this article.]

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“…Rabbit polyclonal antibodies to RhAG, Glut1, GPA, CD47, 29,30 SEC24C, 31 SEC24D 32 and SEC31A 31 were available in house. Anti-mouse band 3 was from Prof. Carsten Wagner (University of Zurich), anti GM130 (BD Transduction), anti-GAPDH (Santa Cruz) and anti-GRP78 (Sigma).…”

Section: Antibodiesmentioning

confidence: 99%

Characteristic phenotypes associated with congenital dyserythropoietic anemia (type II) manifest at different stages of erythropoiesis

Satchwell¹,

Pellegrin²,

Bianchi

et al. 2013

Haematologica

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Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development

Cited by 155 publications

References 40 publications

Enhancement of Procollagen Biosynthesis by p180 through Augmented Ribosome Association on the Endoplasmic Reticulum in Response to Stimulated Secretion

Enhancement of Procollagen Biosynthesis by p180 through Augmented Ribosome Association on the Endoplasmic Reticulum in Response to Stimulated Secretion

A lacZ reporter gene expression atlas for 313 adult KOMP mutant mouse lines

Characteristic phenotypes associated with congenital dyserythropoietic anemia (type II) manifest at different stages of erythropoiesis

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