Genetic Analyses of Integrin Signaling

Wickström, Sara A.; Radovanac, Korana; Fässler, Reinhard

doi:10.1101/cshperspect.a005116

Cited by 91 publications

(79 citation statements)

References 158 publications

(150 reference statements)

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“…The effects of deleting integrin-associated proteins resemble, as anticipated, those of integrin loss, and also reveal differences in the extent to which basement membrane adhesion is compromised (see also Wickstrom et al 2011). Thus, Kindlin-1 -deficient mice show skin atrophy and reduced keratinocyte proliferation, consistent with an effect on the epidermal stem cell compartment, but in the absence of epidermal detachment from the basement membrane (Ussar et al 2008).…”

Section: Integrin-ecm Interactions Regulate Stem Cell Fatementioning

confidence: 56%

Cell-Extracellular Matrix Interactions in Normal and Diseased Skin

Watt

Fujiwara²

2011

Cold Spring Harbor Perspectives in Biology

320

269

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Mammalian skin comprises a multi-layered epithelium, the epidermis, and an underlying connective tissue, the dermis. The epidermal extracellular matrix is a basement membrane, whereas the dermal ECM comprises fibrillar collagens and associated proteins. There is considerable heterogeneity in ECM composition within both epidermis and dermis. The functional significance of this extends beyond cell adhesion to a range of cell autonomous and nonautonomous processes, including control of epidermal stem cell fate. In skin, cell-ECM interactions influence normal homeostasis, aging, wound healing, and disease. Disturbed integrin and ECM signaling contributes to both tumor formation and fibrosis. Strategies for manipulating cell-ECM interactions to repair skin defects and intervene in a variety of skin diseases hold promise for the future.

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Section: Integrin-ecm Interactions Regulate Stem Cell Fatementioning

confidence: 56%

Cell-Extracellular Matrix Interactions in Normal and Diseased Skin

Watt

Fujiwara²

2011

Cold Spring Harbor Perspectives in Biology

320

269

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“…Correct assembly of the ECM and signaling from the ECM are central to the normal function of the skin, and inappropriate expression of ECM receptors of the b1 integrin family affects multiple processes, including hair follicle morphogenesis, wound healing and cancer metastasis (Brakebusch and Fässler, 2005;Brakebusch et al, 2000;Legate et al, 2009;Raghavan et al, 2000;Wickström and Fassler, 2009;Wickström et al, 2011). Despite a compensatory upregulation of avb6 integrins, conditional ablation of b1 integrins in skin results in severe blistering and basement membrane defects (Brakebusch et al, 2000;Raghavan et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Uncovering functional differences between kindlin-1 and kindlin-2 in keratinocytes

Bandyopadhyay

Rothschild

Kim

et al. 2012

Journal of Cell Science

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SummaryIntegrin-b1-null keratinocytes can adhere to fibronectin through integrin avb6, but form large peripheral focal adhesions and exhibit defective cell spreading. Here we report that, in addition to the reduced avidity of avb6 integrin binding to fibronectin, the inability of integrin b6 to efficiently bind and recruit kindlin-2 to focal adhesions directly contributes to these phenotypes. Kindlins regulate integrins through direct interactions with the integrin-b cytoplasmic tail and keratinocytes express kindlin-1 and kindlin-2. Notably, although both kindlins localize to focal adhesions in wild-type cells, only kindlin-1 localizes to the integrin-b6-rich adhesions of integrin-b1-null cells. Rescue of these cells with wild-type and chimeric integrin constructs revealed a correlation between kindlin-2 recruitment and cell spreading. Furthermore, despite the presence of kindlin-1, knockdown of kindlin-2 in wild-type keratinocytes impaired cell spreading. Our data reveal unexpected functional consequences of differences in the association of two homologous kindlin isoforms with two closely related integrins, and suggest that despite their similarities, different kindlins are likely to have unique functions.

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“…Subgroups of integrins are defined by binding to collagens, laminins, or RGD amino acid sequences, or by being expressed on leukocytes. Integrin structure and function are discussed elsewhere in this collection and in several reviews (Hynes 2002;Luo et al 2007;Askari et al 2009;Geiger et al 2009;Campbell and Humphries 2011;Wickstrom et al 2011;Geiger and Yamada 2011).…”

Section: Cross Talk Between Integrins and Growth Factorsmentioning

confidence: 99%

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Munger¹,

Sheppard²

2011

Cold Spring Harbor Perspectives in Biology

326

275

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The growth factor TGF-b is secreted in a latent complex consisting of three proteins: TGF-b, an inhibitor (latency-associated protein, LAP, which is derived from the TGF-b propeptide) and an ECM-binding protein (one of the latent TGF-b binding proteins, or LTBPs). LTBPs interact with fibrillins and other ECM components and thus function to localize latent TGF-b in the ECM. LAP contains an integrin-binding site (RGD), and several RGD-binding integrins are able to activate latent TGF-b through binding this site. Mutant mice defective in integrin-mediated activators, and humans and mice with fibrillin gene mutations, show the critical role of ECM and integrins in regulating TGF-b signaling.

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Genetic Analyses of Integrin Signaling

Cited by 91 publications

References 158 publications

Cell-Extracellular Matrix Interactions in Normal and Diseased Skin

Cell-Extracellular Matrix Interactions in Normal and Diseased Skin

Uncovering functional differences between kindlin-1 and kindlin-2 in keratinocytes

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

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