QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online December 11, 2006
doi: 10.1242/10.1242/jcs.03304

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Long, H. A. Articles by Määttä, A. Search for Related Content PubMed PubMed Citation Articles by Long, H. A. Articles by Määttä, A. Social Bookmarking                         What's this?

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

Heather A. Long^*,, Veronika Boczonadi, Lorna McInroy, Martin Goldberg and Arto Määttä

Centre for Stem Cell Research and Regenerative Medicine, School of Biological and Biomedical Sciences, University of Durham, Durham, DH1 3LE, UK

Author for correspondence (e-mail: Arto.Maatta{at}durham.ac.uk)

Accepted 18 October 2006

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.

Key words: Intermediate filaments, Plakins, Epithelial migration, RNA-interference

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D. C.Y. Phua, P. O. Humbert, and W. Hunziker Vimentin Regulates Scribble Activity by Protecting It from Proteasomal Degradation Mol. Biol. Cell, June 15, 2009; 20(12): 2841 - 2855. [Abstract] [Full Text] [PDF]

				K.-h. Yoon and P. G. FitzGerald Periplakin Interactions with Lens Intermediate and Beaded Filaments Invest. Ophthalmol. Vis. Sci., March 1, 2009; 50(3): 1283 - 1289. [Abstract] [Full Text] [PDF]

				N. Ojeh, V. Pekovic, C. Jahoda, and A. Maatta The MAGUK-family protein CASK is targeted to nuclei of the basal epidermis and controls keratinocyte proliferation J. Cell Sci., August 15, 2008; 121(16): 2705 - 2717. [Abstract] [Full Text] [PDF]