Laminin N-terminus α31 regulates keratinocyte adhesion and migration through modifying the organisation and proteolytic processing of laminin 332
Autor: | Valentina Iorio, Liam Shaw, Kazuhiro Yamamoto, Lee D. Troughton, Kevin J. Hamill, Conor J Sugden |
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Rok vydání: | 2019 |
Předmět: |
0303 health sciences
biology Chemistry Hemidesmosome Motility Matrix metalloproteinase Epithelium Cell biology Extracellular matrix Focal adhesion 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Laminin 030220 oncology & carcinogenesis medicine biology.protein Keratinocyte 030304 developmental biology |
DOI: | 10.1101/617597 |
Popis: | Laminin N-terminus α31 (LaNt α31), a member of the laminin superfamily, expressed at low levels in intact epithelium but upregulated during wound repair. Increased expression of LaNt α31 reduced migration rate of corneal keratinocytes through an unknown mechanism. Here, we investigated whether LaNt α31 influences cell behaviour through modulating laminin-mediated processes. Adenoviral delivery of LaNt α31 into corneal epithelial cells led to reduced migration speed and increased cell spreading and changed laminin 332 organisation from diffuse arcs to tight clusters. Enhanced recruitment of collagen XVII and bullous pemphigoid antigen 1e to β4 integrin, indicating early maturation of hemidesmosomes, and changed focal adhesion distribution were also identified. LaNt α31 and laminin β3 co-immunoprecipitated from doubly transduced cells and were deposited together in live imaging experiment. Moreover, LaNt α31 expression led to increased matrix metalloproteinase (MMP) activity and proteolytic processing of laminin α3, and the inhibition of MMP activity rescued the laminin and hemidesmosome phenotypes. Provision of cell-derived extracellular matrix rescued the cell spreading and motility effects. These findings reveal LaNt α31 as a new player in regulating cell-to-matrix adhesion through its ability to influence laminin organisation and proteolytic processing. |
Databáze: | OpenAIRE |
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