Integrin endocytosis on elastic substrates mediates mechanosensing

Li, Jing; Chen, Huarong; Xu, Yue; Hu, Jijie; Xie, Fu Qiang; Yang, Chun

doi:10.1016/j.jbiomech.2016.05.024

Cited by 12 publications

(17 citation statements)

References 26 publications

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“…During the recycling of α V β 3 , the RAB11 effector http://Rab-coupling protein (RCP) is bound to β 3 , but in the absence or disturbance of α V β 3 , α 5 β 1 is recycled to the plasma membrane through the interaction of RCP with β 1 , resulting in random migration in 2D and 3D microenvironments [Caswell et al., ]. β 1 , α 1 and α 2 are internalised by endocytosis on collagen I‐coated soft substrates, whereas α 5 and α 6 are not [Li et al., ]. Recycling of α V β 3 integrins is required for force sensing at the cell edge during migration [Roca‐Cusachs et al., ; Haynie, ].…”

Section: Textmentioning

confidence: 99%

Integrin diversity brings specificity in mechanotransduction

Seetharaman

Etienne-Manneville

2018

Biology of the Cell

103

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Cells sense and respond to the biochemical and physical properties of the extracellular matrix (ECM) through adhesive structures that bridge the cell cytoskeleton and the surrounding environment. Integrin-mediated adhesions interact with specific ECM proteins and sense the rigidity of the substrate to trigger signalling pathways that, in turn, regulate cellular processes such as adhesion, motility, proliferation and differentiation. This process, called mechanotransduction, influenced by the involvement of different integrin subtypes and their high ECM-ligand binding specificity, contributes to the cell-type-specific mechanical responses. In this review, we describe how the expression of particular integrin subtypes affects cellular adaptation to substrate rigidity. We then explain the role of integrins and associated proteins in mechanotransduction, focusing on their specificity in mechanosensing and force transmission.

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Section: Textmentioning

confidence: 99%

Integrin diversity brings specificity in mechanotransduction

Seetharaman

Etienne-Manneville

2018

Biology of the Cell

103

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“…An increase in matrix stiffness enhances vascular endothelial growth factor receptor VEGFR-2 internalization, signaling, and proliferation of tumor-like phenotype in endothelial cells [50,51] . Endocytosis of integrin β1 in bone marrow mesenchymal stem cells on collagen I-coated substrates promotes cell differentiation to a neuronal lineage [52] . Thus, cells may utilize endocytic pathways as a mechanosensitive conduit for sensing and responding to changes in ECM.…”

Section: Physical Confinement Of Cells and Mechanical Properties Of Ementioning

confidence: 99%

Mechanical Regulation of Endocytosis: New Insights and Recent Advances

Joseph

Liu

2020

Adv. Biosys.

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Endocytosis is a mechanosensitive process. It involves remodeling of the plasma membrane from a flat shape to a budded morphology, often at the sub-micron scale. This remodeling process is energy-intensive and is influenced by mechanical factors such as membrane tension, membrane rigidity, and physical properties of cargo and extracellular surroundings. The cellular responses to a variety of mechanical factors by distinct endocytic pathways are important for cells to counteract rapid and extreme disruptions in the mechano-homeostasis of cells. Recent advances in microscopy and mechanical manipulation at the cellular scale have led to new discoveries of mechanoregulation of endocytosis by the aforementioned factors. While factors such as membrane tension and membrane rigidity are generally shown to inhibit endocytosis, other mechanical stimuli have complex relationships with endocytic pathways. We are at a juncture where it is now possible to utilize experimental techniques to interrogate theoretical predictions on mechanoregulation of endocytosis in cells and even living organisms.

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“…Statistical significance of between time-point differences was estimated by t -test; N. S., non-significant. (D and E) Experimental schemes for the analysis of endocytosis and recycling followed by ELISA (according to 25 ). (F and H) Net endocytosis of (F) total β1 integrin and (H) active β1-integrin in wild type and Cav1KO MEFs at the time points indicated.…”

Section: Resultsmentioning

confidence: 99%

“…β1-integrin kinetics were analyzed after biotin labeling of cell-surface integrins followed by a capture ELISA-based assay, using a modification of a previously described protocol 25 .…”

Section: Methodsmentioning

confidence: 99%

“…Statistical significance of between time-point differences was estimated by ttest; N. S., non-significant. (D and E) Experimental schemes for the analysis of endocytosis and recycling followed by ELISA (according to 25 ). (F and H) Net endocytosis of (F) total 1 integrin and (H) active 1-integrin in wild type and Cav1KO MEFs TIRF videos revealed that 1-integrins in wild type MEFs as stable, largely immobile structures; in contrast, 1-integrins in Cav1KO MEFs showed a dynamic behavior, rapidly appearing and disappearing from the PM plane (Suppl.…”

Section: Cav1ko Mefs Recycle 1-integrin Faster Than Wild Type Mefsmentioning

confidence: 99%

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Caveolae couple mechanical stress to integrin recycling and activation

Lolo

Pavón

Grande-García

et al. 2022

Preprint

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Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.

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Integrin endocytosis on elastic substrates mediates mechanosensing

Cited by 12 publications

References 26 publications

Integrin diversity brings specificity in mechanotransduction

Integrin diversity brings specificity in mechanotransduction

Mechanical Regulation of Endocytosis: New Insights and Recent Advances

Caveolae couple mechanical stress to integrin recycling and activation

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