Heather A. Long
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
Authors
Veronika Boczonadi
Lorna McInroy
Professor Martin Goldberg m.w.goldberg@durham.ac.uk
Professor
Dr Arto Maatta arto.maatta@durham.ac.uk
Associate Professor
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. |
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