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Periplakin-dependent re-organisation of keratin cytoskeleton and loss of collective migration in Keratin 8 down-regulated epithelial sheets.

Long, H. A. and Boczonadi, V. and McInroy, L. and Goldberg, M. and Maatta, A. (2006) 'Periplakin-dependent re-organisation of keratin cytoskeleton and loss of collective migration in Keratin 8 down-regulated epithelial sheets.', Journal of cell science., 119 (24). pp. 5147-5159.

Abstract

Collective migration of epithelial sheets requires maintenance of cell-cell junctions and co-ordination of the movement of the migrating front. We have investigated the role of keratin intermediate filaments and periplakin, a cytoskeletal linker protein, in the migration of simple epithelial cells. Scratch wounding induces bundling of keratins into a cable of tightly packed filaments adjacent to the free wound edge. Keratin re-organisation is preceded by a re-distribution of periplakin away from the free wound edge. Periplakin participates with dynamic changes in the keratin cytoskeleton via its C-terminal linker domain that co-localises with okadaic-acid-treated keratin granules. Stable expression of the periplakin C-terminal domain increases keratin bundling and Ser431 keratin phosphorylation at wound edge resulting in a delay in wound closure. Ablation of periplakin by siRNA inhibits keratin cable formation and impairs wound closure. Knockdown of keratin 8 with siRNA results in (1) a loss of desmoplakin localisation at cell borders, (2) a failure of MCF-7 epithelial sheets to migrate as a collective unit and (3) accelerated wound closure in vimentin-positive HeLa and Panc-1 cell lines. Thus, keratin 8 is required for the maintenance of epithelial integrity during migration and periplakin participates in the re-organisation of keratins in migrating cells.

Item Type:Article
Keywords:Intermediate filaments, Plakins, Epithelial migration, RNA-interference.
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1242/jcs.03304
Date accepted:18 October 2006
Date deposited:11 May 2018
Date of first online publication:11 December 2006
Date first made open access:No date available

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