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β4 Integrin Regulates the Migration of Alveolar Epithelial Cells
Başlık:
β4 Integrin Regulates the Migration of Alveolar Epithelial Cells
Yazar:
Colburn, Zachary T., author. (orcid)0000-0003-1280-7613
ISBN:
9780438104099
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (179 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Jonathan C.R. Jones Committee members: Kwanhee Kim; Eric Shelden; Bertrand Tanner.
Özet:
Cell migration regulates crucial biological processes including development, wound healing, and metastasis. It requires the coordination of signaling and cytoskeletal rearrangements as well as the interactions between extracellular matrix ligands and matrix receptor proteins. Integrins are transmembrane matrix receptor proteins that link the extracellular matrix to the cytoskeleton. They form heterodimers composed of one alpha and one beta integrin subunit and cluster together to form large adhesion complexes. Most integrins are found in matrix adhesion structures termed focal adhesions. However, the integrin heterodimer alpha6beta4 assembles into distinct adhesion structures. These include hemidesmosomes, which mediate attachment of the epidermis to the dermis, as well as punctate arrays found in some epithelial and endothelial cells. Interestingly, the role of beta4 integrin in cell migration is controversial, with studies reporting contradictory functions, which may be the result of cell or tissue specific differences. We investigated the functions and regulatory mechanisms of beta4 integrin in the migration of lung epithelial cells.
In the lung epithelial cell line A549 alpha6beta4 integrin localizes in punctate arrays predominantly in lamellipodia. Surprisingly, in beta4 integrin knockdown cells the distribution of alpha6 integrin is unperturbed. In such cells, alpha6 integrin instead pairs with beta1 integrin. Since beta1 integrin typically localizes to focal adhesions this represents a possible method of cross talk between distinct types of adhesion structures. In addition, beta4 integrin knockdown cells exhibit reductions in Rac1 activity and directed migration, which can be restored following infection with adenoviruses encoding either beta4 integrin or constitutively active Rac1. Interestingly, we have found that beta4 integrin promotes the leader cell phenotype since its expression in the leading edge of wounded epithelial sheets is sufficient to drive wound closure We have also determined that beta4 integrin associates with vimentin filaments in these cells. Moreover, vimentin knockdown cells exhibit reduced Rac1 activity and cell migration.
In summary, these results indicate that beta4 integrin is a positive regulator of both directed single cell migration and collective cell migration in lung epithelial cells. It does so by regulating signaling which depends on its association with vimentin intermediate filaments.
Notlar:
School code: 0251
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(689322.1) | 689322-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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