Focal adhesion disassembly requires clathrin‐dependent endocytosis of integrins

Chao, Wei‐Ting; Kunz, Jeannette

doi:10.1016/j.febslet.2009.03.037

Cited by 188 publications

(200 citation statements)

References 26 publications

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“…As integrins are a major component of focal adhesions, their removal is an integral part of focal adhesion disassembly. While the protease calpain contributes to this by cleaving focal adhesion proteins like integrins and talin [85], dynamin and CME of active b1 integrins were also shown to be instrumental for this process [72,86]. Proteins of the endocytic machinery like clathrin, AP-2, Dab2 and dynamin2 localize to adhesion sites prior to adhesion disassembly.…”

Section: Focal Adhesion Disassemblymentioning

confidence: 99%

“…Proteins of the endocytic machinery like clathrin, AP-2, Dab2 and dynamin2 localize to adhesion sites prior to adhesion disassembly. The importance of CME for focal adhesion disassembly is highlighted by the fact that depletion of dynamin2 blocks b1 integrin internalization leading to impaired focal adhesion disassembly and consequently to defects in cell migration [86]. CME depends on phosphatidylinositol (4,5)bisphosphate [PI(4,5)P 2 ] which is generated by the enzyme PIPK1b and contributes to the recruitment of endocytic proteins like AP-2.…”

Section: Focal Adhesion Disassemblymentioning

confidence: 99%

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On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

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Section: Focal Adhesion Disassemblymentioning

confidence: 99%

Section: Focal Adhesion Disassemblymentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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“…43 Several reports demonstrate a role for NO in clathrin-and dynaminmediated endocytosis and also integrins can be endocytosed by these pathways. [27][28][29]44 NO S-nitrosylates dynamin increasing dynamin oligomerization and GTPase activity, thereby increasing endocytosis. 33 Our results support a role for dynamin in ILK internalization because a specific inhibitor of dynamin activation reversed ILK degradation and localization in endosomes and later in lysosomes, thus proving that NO drives ILK endocytosis to direct ILK to lysosome degradation.…”

Section: Discussionmentioning

confidence: 99%

“…26 Thus, we sought to investigate whether NO Endocytosis of integrins and associated proteins can be accomplished by chlatrin-dependent, caveolae-dependent, and noncaveolae-mediated pathways. [27][28][29] The first 2 processes rely on the GTPase dynamin for the scission of endocytic intermediates to generate early endosomes. 30 Previous studies have demonstrated that NO can stimulate endocytosis by S-nytrosilation of dynamin.…”

Section: No Triggers Ilk Endocytosis Through a Dynamin-dependent Pathwaymentioning

confidence: 99%

iNOS-Derived Nitric Oxide Induces Integrin-Linked Kinase Endocytic Lysosome-Mediated Degradation in the Vascular Endothelium

Reventún

Alique

Cuadrado

et al. 2017

ATVB

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Objective-ILK (integrin-linked kinase) plays a key role in controlling vasomotor tone and is decreased in atherosclerosis.The objective of this study is to test whether nitric oxide (NO) regulates ILK in vascular remodeling. Approach and Results-We found a striking correlation between increased levels of inducible nitric oxide and decreased ILK levels in human atherosclerosis and in a mouse model of vascular remodeling (carotid artery ligation) comparing with iNOS (inducible NO synthase) knockout mice. iNOS induction produced the same result in mouse aortic endothelial cells, and these effects were mimicked by an NO donor in a time-dependent manner. We found that NO decreased ILK protein stability by promoting the dissociation of the complex ILK/Hsp90 (heat shock protein 90)/eNOS (endothelial NO synthase), leading to eNOS uncoupling. NO also destabilized ILK signaling platform and lead to decreased levels of paxillin and α-parvin. ILK phosphorylation of its downstream target GSK3-β (glycogen synthase kinase 3 beta) was decreased by NO. Mechanistically, NO increased ILK ubiquitination mediated by the E3 ubiquitin ligase CHIP (C terminus of HSC70-interacting protein), but ILK ubiquitination was not followed by proteasome degradation. Alternatively, NO drove ILK to degradation through the endocytic-lysosomal pathway. ILK colocalized with the lysosome marker LAMP-1 (lysosomal-associated membrane protein 1) in endothelial cells, and inhibition of lysosome activity with chloroquine reversed the effect of NO. Likewise, ILK colocalized with the early endosome marker EEA1 (early endosome antigen 1). ILK endocytosis proceeded via dynamin because a specific inhibitor of dynamin (Dyngo 4a) was able to reverse ILK endocytosis and its lysosome degradation. Conclusions-Endocytosis

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“…The lipid second messengers play an important role in this retraction process, with PIP 2 levels remaining high at the cell front to ensure that adapters such as talin are recruited to facilitate the adapter-mediated endocytosis of integrins (Chao et al 2010a). Conversely, to prevent the recruitment of integrin adaptors involved in adhesion site initiation and assembly at the rear of the cell, such as ILK and kindlin, the levels of PIP 3 are kept low (Chao and Kunz 2009;Ezratty et al 2009;Chao et al 2010b). …”

Section: Integrin-mediated Migrationmentioning

confidence: 99%

Structural and mechanical functions of integrins

2013

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Integrins are ubiquitously expressed cell surface receptors that play a critical role in regulating the interaction between a cell and its microenvironment to control cell fate. These molecules are regulated either via their expression on the cell surface or through a unique bidirectional signalling mechanism. However, integrins are just the tip of the adhesome iceberg, initiating the assembly of a large range of adaptor and signalling proteins that mediate the structural and signalling functions of integrin. In this review, we summarise the structure of integrins and mechanisms by which integrin activation is controlled. The different adhesion structures formed by integrins are discussed, as well as the mechanical and structural roles integrins play during cell migration. As the function of integrin signalling can be quite varied based on cell type and context, an in depth understanding of these processes will aid our understanding of aberrant adhesion and migration, which is often associated with human pathologies such as cancer.

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Focal adhesion disassembly requires clathrin‐dependent endocytosis of integrins

Cited by 188 publications

References 26 publications

On the move: endocytic trafficking in cell migration

On the move: endocytic trafficking in cell migration

iNOS-Derived Nitric Oxide Induces Integrin-Linked Kinase Endocytic Lysosome-Mediated Degradation in the Vascular Endothelium

Structural and mechanical functions of integrins

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