Collagen I matrix turnover is regulated by fibronectin polymerization

Shi, Feng; Harman, Jennifer L.; Fujiwara, Keigi; Sottile, Jane

doi:10.1152/ajpcell.00341.2009

Cited by 87 publications

(72 citation statements)

References 72 publications

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“…The endocytosis and trafficking of ECM receptors, particularly that of the integrins, have been studied extensively and are known to play important roles in cytokinesis and cell migration (Caswell et al, 2009). Among ECM molecules, fibronectin, collagen-I and vitronectin have been reported to undergo endocytosis, with internalization mediated, in part, by the integrins (Madsen et al, 2011;Memmo and McKeown-Longo, 1998;Shi et al, 2010;Shi and Sottile, 2008;Sottile and Chandler, 2005). However, the endocytosis and trafficking of laminins and other basement membrane proteins is not understood at the level of mediators, pathways or biological significance, despite these being crucial structural and signaling molecules that contact the majority of cells in metazoans (Yurchenco, 2011).…”

Section: Discussionmentioning

confidence: 99%

Endocytic trafficking of laminin is controlled by dystroglycan and disrupted in cancers

Leonoudakis

Huang

Akhavan

et al. 2014

Journal of Cell Science

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The dynamic interactions between cells and basement membranes serve as essential regulators of tissue architecture and function in metazoans, and perturbation of these interactions contributes to the progression of a wide range of human diseases, including cancers. Here, we reveal the pathway and mechanism for the endocytic trafficking of a prominent basement membrane protein, laminin-111 (referred to here as laminin), and their disruption in disease. Livecell imaging of epithelial cells revealed pronounced internalization of laminin into endocytic vesicles. Laminin internalization was receptor mediated and dynamin dependent, and laminin proceeded to the lysosome through the late endosome. Manipulation of laminin receptor expression revealed that the dominant regulator of laminin internalization is dystroglycan, a laminin receptor that is functionally perturbed in muscular dystrophies and in many cancers. Correspondingly, laminin internalization was found to be deficient in aggressive cancer cells displaying non-functional dystroglycan, and restoration of dystroglycan function strongly enhanced the endocytosis of laminin in both breast cancer and glioblastoma cells. These results establish previously unrecognized mechanisms for the modulation of cell-basement-membrane communication in normal cells and identify a profound disruption of endocytic laminin trafficking in aggressive cancer subtypes.

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Section: Discussionmentioning

confidence: 99%

Endocytic trafficking of laminin is controlled by dystroglycan and disrupted in cancers

Leonoudakis

Huang

Akhavan

et al. 2014

Journal of Cell Science

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“…MT1-MMP is involved in turnover and endocytosis of matrix collagen I, but not matrix fibrinogen Our previous data showed that loss of ECM fibronectin results in the loss of several other proteins from the ECM, including collagen I (Shi et al, 2010;Sottile and Hocking, 2002). Therefore, we investigated whether MT1-MMP is involved in turnover of other ECM proteins.…”

Section: Mt1-mmp Is Involved In Ecm Fibronectin Turnover and Endocytosismentioning

confidence: 94%

“…Texas Red, Alexa-Fluor-488-and AlexaFluor-633-conjugated fibronectins were made according to the manufacture's protocol (Molecular Probes/Invitrogen). Texas Red-conjugated collagen I was made as described previously (Shi et al, 2010). pUR4, a fibronectin polymerization inhibitor, was prepared as described previously (Chiang et al, 2009).…”

Section: Immunological Reagents Chemicals and Proteinsmentioning

confidence: 99%

MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin

Shi

Sottile

2011

Journal of Cell Science

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111

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SummaryThe extracellular matrix (ECM) is dynamically remodeled by cells during development, normal tissue homeostasis and in a variety of disease processes. We previously showed that fibronectin is an important regulator of ECM remodeling. The deposition and/or polymerization of fibronectin into the ECM controls the deposition and stability of other ECM molecules. In addition, agents that inhibit fibronectin polymerization promote the turnover of fibronectin fibrils and enhance ECM fibronectin endocytosis and intracellular degradation. Endocytosis of ECM fibronectin is regulated by b1 integrins, including a5b1 integrin. We have examined the role of extracellular proteases in regulating ECM fibronectin turnover. Our data show that membrane type matrix metalloproteinase 1 (MT1-MMP; also known as MMP14) is a crucial regulator of fibronectin turnover. Cells lacking MT1-MMP show reduced turnover and endocytosis of ECM fibronectin. MT1-MMP regulates ECM fibronectin remodeling by promoting extracellular cleavage of fibronectin and by regulating a5b1-integrin endocytosis. Our data also show that fibronectin polymerization stabilizes fibronectin fibrils and inhibits ECM fibronectin endocytosis by inhibiting a5b1-integrin endocytosis. These data are the first to show that an ECM protein and its modifying enzyme can regulate integrin endocytosis. These data also show that integrin trafficking plays a major role in modulating ECM fibronectin remodeling. The dual dependence of ECM fibronectin turnover on extracellular proteolysis and endocytosis highlights the complex regulatory mechanisms that control ECM remodeling to ensure maintenance of proper tissue function.

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“…4). Collagen phagocytosis has been studied through the use of collagen-coated beads or native fibrillar collagen (156) and is dependent on the ␣ 2 ␤ 1 integrin (3,24,93). Fibroblasts using this integrin receptor bind and internalize collagen through a Gelsolin-and Racdependent pathway (2).…”

Section: Intracellular Pathway Of Collagen Degradationmentioning

confidence: 99%

Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis

McKleroy

Lee

Atabai

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

210

169

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Pulmonary fibrosis is a vexing clinical problem with no proven therapeutic options. In the normal lung there is continuous collagen synthesis and collagen degradation, and these two processes are precisely balanced to maintain normal tissue architecture. With lung injury there is an increase in the rate of both collagen production and collagen degradation. The increase in collagen degradation is critical in preventing the formation of permanent scar tissue each time the lung is exposed to injury. In pulmonary fibrosis, collagen degradation does not keep pace with collagen production, resulting in extracellular accumulation of fibrillar collagen. Collagen degradation occurs through both extracellular and intracellular pathways. The extracellular pathway involves cleavage of collagen fibrils by proteolytic enzyme including the metalloproteinases. The less-well-described intracellular pathway involves binding and uptake of collagen fragments by fibroblasts and macrophages for lysosomal degradation. The relationship between these two pathways and their relevance to the development of fibrosis is complex. Fibrosis in the lung, liver, and skin has been associated with an impaired degradative environment. Much of the current scientific effort in fibrosis is focused on understanding the pathways that regulate increased collagen production. However, recent reports suggest an important role for collagen turnover and degradation in regulating the severity of tissue fibrosis. The objective of this review is to evaluate the roles of the extracellular and intracellular collagen degradation pathways in the development of fibrosis and to examine whether pulmonary fibrosis can be viewed as a disease of impaired matrix degradation rather than a disease of increased matrix production.

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Collagen I matrix turnover is regulated by fibronectin polymerization

Cited by 87 publications

References 72 publications

Endocytic trafficking of laminin is controlled by dystroglycan and disrupted in cancers

Endocytic trafficking of laminin is controlled by dystroglycan and disrupted in cancers

MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin

Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis

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