Desmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination

Oxana Nekrasova, Robert M. Harmon, Joshua A. Broussard, Jennifer L. Koetsier, Lisa M. Godsel, Gillian N. Fitz, Margaret L. Gardel and Kathleen J. Green ()
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Oxana Nekrasova: Northwestern University Feinberg School of Medicine
Robert M. Harmon: Northwestern University Feinberg School of Medicine
Joshua A. Broussard: Northwestern University Feinberg School of Medicine
Jennifer L. Koetsier: Northwestern University Feinberg School of Medicine
Lisa M. Godsel: Northwestern University Feinberg School of Medicine
Gillian N. Fitz: Northwestern University Feinberg School of Medicine
Margaret L. Gardel: University of Chicago
Kathleen J. Green: Northwestern University Feinberg School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: Abstract The epidermis is a multi-layered epithelium that serves as a barrier against water loss and environmental insults. Its morphogenesis occurs through a tightly regulated program of biochemical and architectural changes during which basal cells commit to differentiate and move towards the skin’s surface. Here, we reveal an unexpected role for the vertebrate cadherin desmoglein 1 (Dsg1) in remodeling the actin cytoskeleton to promote the transit of basal cells into the suprabasal layer through a process of delamination, one mechanism of epidermal stratification. Actin remodeling requires the interaction of Dsg1 with the dynein light chain, Tctex-1 and the actin scaffolding protein, cortactin. We demonstrate that Tctex-1 ensures the correct membrane compartmentalization of Dsg1-containing desmosomes, allowing cortactin/Arp2/3-dependent perijunctional actin polymerization and decreasing tension at E-cadherin junctions to promote keratinocyte delamination. Moreover, Dsg1 is sufficient to enable simple epithelial cells to exit a monolayer to form a second layer, highlighting its morphogenetic potential.

Date: 2018
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DOI: 10.1038/s41467-018-03414-6

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