Knockdown of p180 Eliminates the Terminal Differentiation of a Secretory Cell Line

Benyamini, Payam; Webster, Paul; Meyer, David I.

doi:10.1091/mbc.e08-07-0682

Cited by 38 publications

(45 citation statements)

References 66 publications

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“…Previous studies demonstrated potential functions for p180 in rough ER membrane biogenesis and mRNA stabilization, based on overexpression of canine p180 constructs in yeast (17,18) and morphological evaluations of p180-depleted THP-1 cells during differentiation (19). Although elevated p180 protein levels are accompanied by increased production of rough ER as the common output data, our findings are distinct from these reports regarding ER membrane proliferation.…”

Section: Discussioncontrasting

confidence: 68%

“…In contrast, our data for HEL fibroblasts demonstrate that the change in the ER membrane amounts was minimal when p180 was either up-regulated upon ascorbate stimulation or depleted by siRNA targeting, as reported recently (16,21). Instead, we found that the biosynthetic activity for procollagens was reduced without significant loss of mRNAs or perturbation of the ER to Golgi traffic, again in contrast to data for THP-1 cells, which showed impaired apoE secretion because of aberrant intracellular trafficking upon p180 depletion (19).…”

Section: Discussionsupporting

confidence: 57%

“…Based on overexpression experiments in yeast cells, which lack p180 protein, potential functions for p180 in the secretory process have been proposed that involve stabilization of mRNAs and ER membrane proliferation (17,18). A recent study further addressed the roles of p180 in macrophage-like differentiation, and clearly demonstrated a key function for p180 in acquiring the secretory phenotype (19). Contrary to this report, p180 overexpression in a pancreatic islet ␤-cell line failed to enhance amylin secretion despite increased ER membranes (20), indicating the still undefined functions for p180 in the secretory process.…”

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confidence: 99%

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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: Discussioncontrasting

confidence: 68%

Section: Discussionsupporting

confidence: 57%

mentioning

confidence: 99%

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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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“…Additionally, the expression of Rrbp1 was increased nearly 2 fold following 1 week of overload in satellite cell-depleted muscle (Supplemental Table 3), so we selected it for further study. Rrbp1 is highly expressed and necessary for secretory activity in cells such as fibroblasts (Benyamini et al, 2009; Ueno et al, 2010); knockdown of Rrbp1 levels leads to a dramatic decrease in procollagen biosynthesis in fibroblasts (Ueno et al, 2010). Following culture of fibrogenic cells with MPC exosomes, we found no change in Rrbp1 mRNA expression but did observe a decrease in Rrbp1 protein content (Figure 3B–C).…”

Section: Resultsmentioning

confidence: 99%

Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy

et al. 2017

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Summary Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells which influence satellite cell activity and muscle repair during hypertrophy and aging. Here, we show MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206 which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation.

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“…In support of this theory, addition of drugs that dislocate polyribosomes from ER membranes causes a reduction in the amount of cisternal peripheral ER (Puhka et al 2007). Conversely, the amount of cisternal peripheral ER increases when an integral ER membrane protein that binds ribosomes, p180, is overexpressed (Benyamini et al 2009;Shibata et al 2010). Climp63 is another integral ER membrane protein that plays a role in regulating the shape of ER cisternae ( Fig.…”

mentioning

confidence: 99%

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

English

Voeltz

2013

Cold Spring Harbor Perspectives in Biology

278

220

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The endoplasmic reticulum (ER) is a large, continuous membrane-bound organelle comprised of functionally and structurally distinct domains including the nuclear envelope, peripheral tubular ER, peripheral cisternae, and numerous membrane contact sites at the plasma membrane, mitochondria, Golgi, endosomes, and peroxisomes. These domains are required for multiple cellular processes, including synthesis of proteins and lipids, calcium level regulation, and exchange of macromolecules with various organelles at ER-membrane contact sites. The ER maintains its unique overall structure regardless of dynamics or transfer at ER-organelle contacts. In this review, we describe the numerous factors that contribute to the structure of the ER.T he endoplasmic reticulum (ER) is a dynamic organelle responsible for many cellular functions, including the synthesis of proteins and lipids, and regulation of intracellular calcium levels. This review focuses on the distinct and complex morphology of the ER. The structure of the ER is complex because of the numerous distinct domains that exist within one continuous membrane bilayer. These domains are shaped by interactions with the cytoskeleton, by proteins that stabilize membrane shape, and by a homotypic fusion machinery that allows the ER membrane to maintain its continuity and identity. The ER also contains domains that contact the plasma membrane (PM) and other organelles including the Golgi, endosomes, mitochondria, lipid droplets, and peroxisomes. ER contact sites with other organelles and the PM are both abundant and dispersed throughout the cytoplasm, suggesting that they too could influence the overall architecture of the ER. As we will discuss here, ER shape and distribution are regulated by many intrinsic and extrinsic forces. ER STRUCTURE AND FORMATION Domains of the ER Are Stabilized by Membrane-Shaping ProteinsThe endoplasmic reticulum (ER) is a large membrane-bound compartment spread throughout the cytoplasm of eukaryotic cells. It is divided into three major morphologies that include the nuclear envelope (NE), peripheral ER cisternae, and an interconnected tubular network

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Knockdown of p180 Eliminates the Terminal Differentiation of a Secretory Cell Line

Cited by 38 publications

References 66 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

Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

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