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bioRxiv · 10.1101/617597

LaNt α31 modulates LM332 organisation during matrix deposition leading to cell-matrix adhesion and migration defects.

Iorio, V.·Troughton, L. D.·Barrera, V.·Hamill, K.
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Abstract

Laminin N-terminus 31 (LaNt 31), a member of the laminin superfamily, expressed at low levels in intact epithelium but upregulated during wound repair. Increased expression of LaNt 31 reduced migration rate of corneal keratinocytes through an unknown mechanism. Here, we investigated whether LaNt 31 influences cell behaviour through modulating laminin-mediated processes. Adenoviral delivery of LaNt 31 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 {beta}4 integrin, indicating early maturation of hemidesmosomes, and changed focal adhesion distribution were also identified. LaNt 31 and laminin {beta}3 co-immunoprecipitated from doubly transduced cells and were deposited together in live imaging experiment. Moreover, LaNt 31 expression led to increased matrix metalloproteinase (MMP) activity and proteolytic processing of laminin 3, 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 31 as a new player in regulating cell-to-matrix adhesion through its ability to influence laminin organisation and proteolytic processing.

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Iorio, V., Troughton, L. D., Barrera, V., Hamill, K.. 2019-04-24. LaNt α31 modulates LM332 organisation during matrix deposition leading to cell-matrix adhesion and migration defects.. https://doi.org/10.1101/617597

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