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

Long, Heather A.; Boczonadi, Veronika; McInroy, Lorna; Goldberg, Martin; Maatta, Arto

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.

Citation

Long, H. A., Boczonadi, V., McInroy, L., Goldberg, M., & 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), 5147-5159. https://doi.org/10.1242/jcs.03304

• Journal Article Type: Article
• Acceptance Date: Oct 18, 2006
• Online Publication Date: Dec 11, 2006
• Publication Date: Dec 15, 2006
• Deposit Date: Feb 22, 2008
• Publicly Available Date: May 11, 2018
• Journal: Journal of Cell Science
• Print ISSN: 0021-9533
• Electronic ISSN: 1477-9137
• Publisher: The Company of Biologists
• Peer Reviewed: Peer Reviewed
• Volume: 119
• Issue: 24
• Pages: 5147-5159
• DOI: https://doi.org/10.1242/jcs.03304
• Keywords: Intermediate filaments, Plakins, Epithelial migration, RNA-interference.
• Public URL: https://durham-repository.worktribe.com/output/1551591