Focal Contacts as Mechanosensors

Riveline, Daniel; Zamir, Eli; Balaban, Nathalie Q.; Schwarz, Ulrich S.; Ishizaki, Toshimasa; Narumiya, Shuh; Kam, Zvi; Geiger, Benjamin; Bershadsky, Alexander D.

doi:10.1083/jcb.153.6.1175

Cited by 1,300 publications

(631 citation statements)

References 79 publications

(118 reference statements)

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“…Since strength of adhesion has been correlated to FA size (Riveline et al , 2001), taken together these data suggest that integrin β1‐mediated binding to laminin 511 supports stronger endothelial cell anchorage to the underlying basement membrane in resistance arteries than laminin 411.…”

Section: Resultsmentioning

confidence: 94%

Endothelial basement membrane laminin 511 is essential for shear stress response

Russo¹,

Luik²,

Yousif³

et al. 2016

The EMBO Journal

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Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM‐1 and VE‐cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical stiffness of arterial endothelium in vivo, smaller integrin β1‐positive/vinculin‐positive focal adhesions, and reduced junctional association of actin–myosin II. In vitro assays reveal that β1 integrin‐mediated interaction with laminin 511 results in high strengths of adhesion, which promotes p120 catenin association with VE‐cadherin, stabilizing it at cell junctions and increasing cell–cell adhesion strength. This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries.

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Section: Resultsmentioning

confidence: 94%

Endothelial basement membrane laminin 511 is essential for shear stress response

Russo¹,

Luik²,

Yousif³

et al. 2016

The EMBO Journal

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“…An attractive possibility is that the interconnecting F-actin filaments associated with the sealing zone apply pulling forces onto the podosomes associated with the outer circumference of the sealing zone. Similar to other integrin adhesions [34][35][36][37][38][39][40], these forces might enhance podosome assembly in these areas, and thus support ring expansion. The structural integrity of the ring depends on the fine balance between the formation and maturation of new podosomal rings and the outward extension rate.…”

Section: Discussionmentioning

confidence: 99%

Effects of surface microtopography on the assembly of the osteoclast resorption apparatus

Geblinger

Zink

Spencer

et al. 2011

J. R. Soc. Interface.

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Bone degradation by osteoclasts depends on the formation of a sealing zone, composed of an interlinked network of podosomes, which delimits the degradation lacuna into which osteoclasts secrete acid and proteolytic enzymes. For resorption to occur, the sealing zone must be coherent and stable for extended periods of time. Using titanium roughness gradients ranging from 1 to 4.5 mm R a as substrates for osteoclast adhesion, we show that microtopographic obstacles of a length scale well beyond the range of the 'footprint' of an individual podosome can slow down sealing-zone expansion. A clear inverse correlation was found between ring stability, structural integrity and sealing-zone translocation rate. Direct live-cell microscopy indicated that the expansion of the sealing zone is locally arrested by steep, three-dimensional 'ridge-like barriers', running parallel to its perimeter. It was, however, also evident that the sealing zone can bypass such obstacles, if pulled by neighbouring regions, extending through flanking, obstacle-free areas. We propose that sealing-zone dynamics, while being locally regulated by surface roughness, are globally integrated via the associated actin cytoskeleton. The effect of substrate roughness on osteoclast behaviour is significant in relation to osteoclast function under physiological and pathological conditions, and may constitute an important consideration in the design of advanced bone replacements.

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“…Consistent with its role in actin polymerization in hair cells of the ear, naturally occurring mutations in mDia1 cause nonsyndromic deafness in humans (32). mDia1 was also recently found to be essential for mechanotransduction in response to integrin activation in SV-80 human fibroblast cells (33) but is not involved in the regulation of integrin-mediated cell adhesion in Jurkat cells (34). In conclusion, mDia1 appears to serve several basic cellular functions ranging from mechanosensation to cytokinesis through a possible effect on cytoskeletal organization.…”

mentioning

confidence: 87%

“…Horseradish peroxidase-conjugated secondary antibodies were used at 1:10,000 followed by enhanced chemiluminescent detection after Western blotting. Immunoprecipitations using IgG-tagged constructs (sIg.7, sIg.7-PKD2/Gln 743 -Glu 871 , or sIg.7-PKD2/Ile 679 -Val 968 ) were done as described earlier (6,33). GFP-tagged mDia1 fusion proteins were detected with a rabbit polyclonal antibody against GFP at 1:500.…”

Section: Methodsmentioning

confidence: 99%

PKD2 Interacts and Co-localizes with mDia1 to Mitotic Spindles of Dividing Cells

Rundle

Gorbsky

Tsiokas

2004

Journal of Biological Chemistry

110

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Mutations in pkd2 result in the type 2 form of autosomal dominant polycystic kidney disease, which accounts for ϳ15% of all cases of the disease. PKD2, the protein product of pkd2, belongs to the transient receptor potential superfamily of cation channels, and it can function as a mechanosensitive channel in the primary cilium of kidney cells, an intracellular Ca 2؉ release channel in the endoplasmic reticulum, and/or a nonselective cation channel in the plasma membrane. We have identified mDia1/Drf1 (mammalian Diaphanous or Diaphanous-related formin 1 protein) as a PKD2-interacting protein by yeast two-hybrid screen. mDia1 is a member of the RhoA GTPase-binding formin homology protein family that participates in cytoskeletal organization, cytokinesis, and signal transduction. We show that mDia1 and PKD2 interact in native and in transfected cells, and binding is mediated by the cytoplasmic C terminus of PKD2 binding to the mDia1 N terminus. The interaction is more prevalent in dividing cells in which endogenous PKD2 and mDia1 co-localize to the mitotic spindles. RNA interference experiments reveal that endogenous mDia1 knockdown in HeLa cells results in the loss of PKD2 from mitotic spindles and alters intracellular Ca 2؉ release. Our results suggest that mDia1 facilitates the movement of PKD2 to a centralized position during cell division and has a positive effect on intracellular Ca 2؉ release during mitosis. This may be important to ensure equal segregation of PKD2 to the daughter cell to maintain a necessary level of channel activity. Alternatively, PKD2 channel activity may be important in the cell division process or in cell fate decisions after division.

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Focal Contacts as Mechanosensors

Cited by 1,300 publications

References 79 publications

Endothelial basement membrane laminin 511 is essential for shear stress response

Endothelial basement membrane laminin 511 is essential for shear stress response

Effects of surface microtopography on the assembly of the osteoclast resorption apparatus

PKD2 Interacts and Co-localizes with mDia1 to Mitotic Spindles of Dividing Cells

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