The Kindlin protein family: new members to the club of focal adhesion proteins

Meves, Alexander; Stremmel, Christopher; Gottschalk, Kay E.; Fässler, Reinhard

doi:10.1016/j.tcb.2009.07.006

Cited by 145 publications

(137 citation statements)

References 61 publications

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“…Previous to this work, Kin-1 loss was known to induce keratinocyte adhesion, spreading and migration defects that were attributed to impaired integrin activation 22 . Ubiquitous Kin-1 loss in the mouse results in perinatal lethality due to severe intestinal dysfunction, with the detachment of colonic epithelium as a result of impaired integrin activation 6 .…”

Section: Discussionmentioning

confidence: 92%

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

et al. 2013

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Kindlin-1 binds to integrins and regulates integrin activation at cell adhesions. Here we report a new function of Kindlin-1 in regulating spindle assembly. We show that Kindlin-1 localizes to centrosomes, its concentration peaking during G2/M, where it associates with various pericentriolar material proteins, including Polo-like kinase 1. Short interfering RNA-mediated depletion of Kindlin-1 increases formation of abnormal mitotic spindles and decreases cellular survival. This effect is dependent not only on the ability of Kindlin-1 to bind integrins but also on Polo-like kinase 1-mediated Kindlin-1 phosphorylation. We demonstrate that a subcellular pool of phosphorylated Kindlin-1 is located exclusively at centrosomes. Our work identifies a novel cellular role for Kindlin-1 in ensuring mitotic spindle assembly and cellular survival that is controlled by phosphorylation via Polo-like kinase 1.

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Section: Discussionmentioning

confidence: 92%

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

et al. 2013

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“…1 The three known family members localize to integrin adhesion sites in cells but have different tissue expression patterns. [2][3][4] Kindlin-2 is expressed in embryonic stem cells and almost ubiquitously in tissues, whereas kindlin-1 is restricted to epithelial and kindlin-3 to hematopoietic and endothelial cells.…”

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confidence: 99%

“…3,5 The biological relevance of kindlins has been examined through in vitro biochemical, cell-based, and functional assays, as well as in mouse models, and their importance is highlighted through their association with several human genetic disorders. 1 Kindlin-1 defects cause the Kindler syndrome (KS), a form of inherited epidermolysis bullosa that manifests with skin blistering, photosensitivity, and progressive generalized poikiloderma. 6,7 Mutations in kindlin-3 cause leukocyte adhesion deficiency type 3, a rare inherited disease characterized by severe bleeding and impaired adhesion of leukocytes to inflamed epithelia.…”

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confidence: 99%

“…6,7 Mutations in kindlin-3 cause leukocyte adhesion deficiency type 3, a rare inherited disease characterized by severe bleeding and impaired adhesion of leukocytes to inflamed epithelia. 1 Thus far, inherited human disorders have not been associated with kindlin-2. 1 Functional similarities between kindlin-1 and kindlin-2 have been postulated, including localization to cell-matrix adhesions and binding to and activation of ␤ 1 and ␤ 3 integrins.…”

mentioning

confidence: 99%

“…1 Thus far, inherited human disorders have not been associated with kindlin-2. 1 Functional similarities between kindlin-1 and kindlin-2 have been postulated, including localization to cell-matrix adhesions and binding to and activation of ␤ 1 and ␤ 3 integrins. 8 -11 In epidermal keratinocytes, kindlin-1 colocalizes with kindlin-2, 12 but whether and how the two kindlins interact with each other have remained unexplored.…”

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confidence: 99%

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Kindlin-1 and -2 Have Overlapping Functions in Epithelial Cells

Esser

Heinemann

et al. 2011

The American Journal of Pathology

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Kindlins are a novel family of intracellular adaptor proteins in integrin-containing focal adhesions. Kindlin-1 and -2 are expressed in the skin, but whether and how they cooperate in adult epithelial cells have remained elusive. We uncovered the overlapping roles of kindlin-1 and -2 in maintaining epithelial integrity and show that the phenotype of kindlin-1-deficient cells can be modulated by regulating kindlin-2 gene expression and vice versa. The experimental evidence is provided by use of human keratinocyte cell lines that express both kindlins, just kindlin-1 or kindlin-2, or none of them. Double deficiency of kindlin-1 and -2 had significant negative effects on focal adhesion formation and actin cytoskeleton organization, cell adhesion, survival, directional migration, and activation of ␤ 1 integrin, whereas deficiency of one kindlin only showed variable perturbation of these functions. Cell motility and formation of cell-cell contacts were particularly affected by lack of kindlin-2. These results predict that kindlin-1 and -2 can functionally compensate for each other, at least in part. The high physiologic and pathologic significance of the compensation was emphasized by the discovery of environmental regulation of kindlin-2 expression. UV-B irradiation induced loss of kindlin-2 in keratinocytes. This first example of environmental regulation of kindlin expression has implications for phenotype modulation in Kindler syndrome, a skin disorder caused by kindlin-1 deficiency.

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Focal Adhesions

Tolbert

Burridge

2011

Cellular Domains

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The Kindlin protein family: new members to the club of focal adhesion proteins

Cited by 145 publications

References 61 publications

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

Kindlin-1 and -2 Have Overlapping Functions in Epithelial Cells

Focal Adhesions

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