We use cookies to ensure that we give you the best experience on our website. By continuing to browse this repository, you give consent for essential cookies to be used. You can read more about our Privacy and Cookie Policy.

Durham Research Online
You are in:

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.


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.
Full text:(VoR) Version of Record
Download PDF
Publisher Web site:
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

Save or Share this output

Look up in GoogleScholar