Kristina Kligys

Northwestern University, Evanston, IL, United States

Are you Kristina Kligys?

Claim your profile

Publications (8)30.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The repair of the bronchiolar epithelium damaged by cell-mediated, physical or chemical insult requires epithelial cell migration over a provisional matrix composed of complexes of extracellular matrix molecules, including fibronectin and laminin. These matrix molecules support migration and enhance cell adhesion. Too much adhesion and cells fail to move, whereas too little adhesion and cells are unable to develop the traction force necessary for motility. Thus, we investigated the relative contributions of laminin and fibronectin to bronchiolar cell adhesion and migration using the immortalized bronchial lung epithelial cell line (BEP2D) and normal human bronchial epithelial (NHBE) cells, both of which assemble a laminin-322/fibronectin-rich matrix. Intriguingly, BEP2D and NHBE cells migrate significantly faster on a laminin-332-rich matrix than on fibronectin. Moreover, addition of fibronectin to laminin-332 matrix suppresses motility of both cell types. Finally, fibronectin enhances the adhesion of both BEP2D and NHBE cells to laminin-332 coated surfaces. These results suggest that fibronectin fine tunes laminin-332-mediated migration by boosting bronchiolar cell adhesion to substrate. We suggest that during epithelial wound healing of the injured airway, fibronectin plays an important adhesive role for laminin-driven epithelial cell motility by promoting a stable cellular interaction with the provisional matrix.
    American Journal of Respiratory Cell and Molecular Biology 04/2013; · 4.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Three major laminin and collagen-binding integrins in skin (α6β4, α3β1, and α2β1) are involved in keratinocyte adhesion to the dermis and dissemination of skin cells during wound healing and/or tumorigenesis. Knockdown of α6 integrin in keratinocytes not only results in motility defects but also leads to decreased surface expression of the α2, α3, and β4 integrin subunits. Whereas α2 integrin mRNA levels are decreased in α6 integrin knockdown cells, α3 and β4 integrin mRNAs levels are unaffected. Expression of either α6 or α3 integrin in α6 integrin knockdown cells restores α2 integrin mRNA levels. Moreover, re-expression of α6 integrin increases β4 integrin protein at the cell surface, which results in an increase in α3 integrin expression via activation of initiation factor 4E-binding protein 1. Our data indicate that the α6β4 integrin is a master regulator of transcription and translation of other integrin subunits and underscore its pivotal role in wound healing and cancer.
    Journal of Biological Chemistry 04/2012; 287(22):17975-84. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Laminins are structural components of basement membranes. In addition, they are key extracellular-matrix regulators of cell adhesion, migration, differentiation and proliferation. This Commentary focuses on a relatively understudied aspect of laminin biology: how is laminin deposited into the extracellular matrix? This topic has fascinated researchers for some time, particularly considering the diversity of patterns of laminin that can be visualized in the matrix of cultured cells. We discuss current ideas of how laminin matrices are assembled, the role of matrix receptors in this process and how laminin-associated proteins modulate matrix deposition. We speculate on the role of signaling pathways that are involved in laminin-matrix deposition and on how laminin patterns might play an important role in specifying cell behaviors, especially directed migration. We conclude with a description of new developments in the way that laminin deposition is being studied, including the use of tagged laminin subunits that should allow the visualization of laminin-matrix deposition and assembly by living cells.
    Journal of Cell Science 12/2009; 122(Pt 24):4409-17. · 5.88 Impact Factor
  • Source
    Kristina Kligys, Jonathan C R Jones
    [Show abstract] [Hide abstract]
    ABSTRACT: Wound healing in the skin requires a compromise between adhesion and migration. Both processes include modulation of the cytoskeleton, cell-surface receptors, and receptor ligands., In this issue, Kopecki et al. demonstrate that overexpression of Flii, an actin-remodeling protein, impedes wound healing but inhibits hemidesmosome formation. In contrast, Flii deficiency results in enhanced wound healing while promoting hemidesmosome assembly. We discuss potential mechanisms that could explain how this unique gelsolin family member might regulate both stable keratinocyte adhesion and motility.
    Journal of Investigative Dermatology 09/2009; 129(8):1856-8. · 6.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Defining the pathways required for keratinocyte cell migration is important for understanding mechanisms of wound healing and tumor cell metastasis. We have recently identified an α6β4 integrin-Rac1 signaling pathway via which the phosphatase Slingshot (SSH) activates/dephosphorylates cofilin, thereby determining keratinocyte migration behavior. Here, we assayed the role of 14-3-3 isoforms in regulating the activity of SSH1. Using amino or carboxy terminal domains of 14-3-3ζ, we demonstrate that in keratinocytes 14-3-3ζ/τ heterodimers bind SSH1, in the absence of Rac1 signaling. This interaction leads to an inhibition of SSH1 activity, as measured by an increase in phosphorylated cofilin levels. Overexpression of the carboxy terminal domain of 14-3-3ζ acts as a dominant negative and inhibits the interaction between 14-3-3τ and SSH1. These results implicate 14-3-3ζ/τ heterodimers as key regulators of SSH1 activity in keratinocytes and suggest they play a role in cytoskeleton remodeling during cell migration.
    Biochemical and Biophysical Research Communications 01/2009; 383(4):450-454. · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent analyses of collagen, elastin and fibronectin matrix assembly, organization and remodeling have been facilitated by the use of tagged proteins that can be visualized without the need for antibody labeling. Here, we report the generation of C-terminal tagged, full-length and "processed" (alpha3DeltaLG4-5) human alpha3 as well as C-terminal tagged, full-length human beta3 laminin subunits in adenoviral vectors. Human epidermal keratinocytes (HEKs) and human bronchial epithelial (BEP2D) cells, which assemble laminin-332-rich matrices, as well as primary rat lung alveolar type II (ATII) cells, which elaborate a fibrous network rich in laminin-311, were infected with adenovirus encoding the tagged human laminin subunits. In HEKs and BEP2D cells, tagged, full-length alpha3, alpha3DeltaLG4-5 and beta3 laminin subunits incorporate into arrays of matrix organized into patterns that are comparable to those observed when such cells are stained using laminin-332 subunit antibody probes. Moreover, HEKs and BEP2Ds move over these tagged, laminin-332-rich matrix arrays. We have also used the tagged beta3 laminin subunit-containing matrices to demonstrate that assembled laminin-332 arrays influence laminin matrix secretion and/or assembly. In the case of rat ATII cells, although tagged alpha3 laminin subunits are not detected in the matrix of rat ATII cells infected with virus encoding full-length human alpha3 laminin protein, processed human alpha3 laminin subunits are incorporated into an extracellular fibrous array. We discuss how these novel laminin reagents can be used to study the organization, processing and assembly of laminin matrices and how they provide new insights into the potential functional importance of laminin fragments.
    Matrix Biology 07/2008; 27(7):640-7. · 3.19 Impact Factor
  • Cell Junctions: Adhesion, Development, and Disease, 04/2008: pages 109 - 133; , ISBN: 9783527622092
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The motility of keratinocytes is an essential component of wound closure and the development of epidermal tumors. In vitro, the specific motile behavior of keratinocytes is dictated by the assembly of laminin-332 tracks, a process that is dependent upon alpha6beta4 integrin signaling to Rac1 and the actin-severing protein cofilin. Here we have analyzed how cofilin phosphorylation is regulated by phosphatases (slingshot (SSH) or chronophin (CIN)) downstream of signaling by alpha6beta4 integrin/Rac1 in human keratinocytes. Keratinocytes express all members of the SSH family (SSH1, SSH2, and SSH3) and CIN. However, expression of phosphatase-dead versions of all three SSH proteins, but not dominant inactive CIN, results in phosphorylation/inactivation of cofilin, changes in actin cytoskeleton organization, loss of cell polarity, and assembly of aberrant arrays of laminin-332 in human keratinocytes. SSH activity is regulated by 14-3-3 protein binding, and intriguingly, 14-3-3/alpha6beta4 integrin protein interaction is required for keratinocyte migration. We wondered whether 14-3-3 proteins function as regulators of Rac1-mediated keratinocyte migration patterns. In support of this hypothesis, inhibition of Rac1 results in an increase in 14-3-3 protein association with SSH. Thus, we propose a novel mechanism in which alpha6beta4 integrin signaling via Rac1, 14-3-3 proteins, and SSH family members regulates cofilin activation, cell polarity, and matrix assembly, leading to specific epidermal cell migration behavior.
    Journal of Biological Chemistry 12/2007; 282(44):32520-8. · 4.65 Impact Factor