The Kindlin protein family: new members to the club of focal adhesion proteins
ABSTRACT Kindlins are a group of proteins that have recently attracted attention for their ability to bind and activate integrins. Moreover, they have also been linked to inherited and acquired human diseases including Kindler syndrome, leukocyte adhesion deficiency, and cancer. Although most studies have focused on kindlins as key regulatory components of cell-extracellular matrix junctions such as focal adhesions, preliminary data suggest the involvement of additional cellular compartments in mediating their functions, particularly at cell-cell contacts and the nucleus. Investigating the many roles of kindlins is likely to expand and sharpen our view on the versatility of integrin-mediated cell adhesion, the nuclear function of focal adhesion proteins, and the crosstalk between cell-cell and cell-matrix adhesions in health and disease.
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- "Kindlin-2 has also been reported to bind to the TGF-β type 1 receptor through its FERM domain and to Smad3 through its N terminus , which mediates this interaction in human kidney tubular epithelial cells . Kindlin-1 and kindlin-2 have also been described to be found in the nucleus of cells; no such localization of kindlin-3 has so far been reported . "
Article: Kindlin-3 in the immune system.[Show abstract] [Hide abstract]
ABSTRACT: Kindlin-3 is a member of the kindlin family of focal adhesion proteins which bind to integrin beta-chain cytoplasmic domains to regulate integrin function. In contrast to kindlin-1 and kindlin-2 proteins, kindlin-3 is expressed mainly in the hematopoietic system. Mutations in kindlin-3 result in the rare genetic disorder, leukocyte adhesion deficiency type III (LAD-III), which is characterized by bleeding and recurrent infections due to deficient beta1, beta2 and beta3 integrin activation in platelets and leukocytes. Here, we review the role of kindlin-3 in integrin activation and in different immune cell functions.01/2014; 3(1):37-42.
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- "Kindlins (kindlin-1, -2, and -3) comprise a family of 3 related proteins that are involved in integrin activation inside cells (Larjava et al., 2008; Meves et al., 2009). Mutations in kind- lin-1 and kindlin-3 are associated with human clinical syndromes (Larjava et al., 2008). "
ABSTRACT: Adhesion of epithelium to the extracellular matrix is crucial for the maintenance of systemic and oral health. In the oral cavity, teeth or artificial dental implants penetrate the soft tissue of the gingiva. In this interface, gingival soft tissue needs to be well attached via the epithelial seal to the tooth or implant surface to maintain health. After injury or wounding, epithelial tissue rapidly migrates to form the initial epithelial cover to restore the barrier against infection. These events are crucially dependent on deposition of extracellular matrix and proper activation and function of integrin receptors in the epithelial cells. Recent experimental evidence suggests that epithelial integrins also participate in the regulation of periodontal inflammation. In this review, we will discuss the structure and function of epithelial integrins and their extracellular ligands and elaborate on their potential role in disease and repair processes in the oral cavity.Journal of dental research 03/2011; 90(12):1367-76. DOI:10.1177/0022034511402207 · 4.14 Impact Factor
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- "However in this biological system, neither kindlin-1 nor kindlin-2 cooperate with the talin head to activate 1 integrins suggesting that kindlins may exert integrin-specific effects (Harburger et al., 2009) (Fig. 1). So far no evidence was provided showing the sequential or the simultaneous binding of talin and kindlin to an individual cytoplasmic tail (Meves et al., 2009; Moser et al., 2009b). Kindlin signaling could interfere with suppressor of integrin activation. "
ABSTRACT: Cells exert actomyosin contractility and cytoskeleton-dependent force in response to matrix stiffness cues. Cells dynamically adapt to force by modifying their behavior and remodeling their microenvironment. This adaptation is favored by integrin activation switch and their ability to modulate their clustering and the assembly of an intracellular hub in response to force. Indeed integrins are mechanoreceptors and mediate mechanotransduction by transferring forces to specific adhesion proteins into focal adhesions which are sensitive to tension and activate intracellular signals. α(5)β(1) integrin is considered of major importance for the formation of an elaborate meshwork of fibronectin fibrils and for the extracellular matrix deposition and remodeling. Here we summarize recent progress in the study of mechanisms regulating the activation cycle of β(1) integrin and the specificity of α(5)β(1) integrin in mechanotransduction.European journal of cell biology 10/2010; 90(2-3):261-9. DOI:10.1016/j.ejcb.2010.09.006 · 3.70 Impact Factor