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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

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


Authors

Heather A. Long

Veronika Boczonadi

Lorna McInroy



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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