Desmosomal cadherin association with Tctex-1 and
cortactin-Arp2/3 drives perijunctional actin
polymerization to promote keratinocyte
, Robert M. Harmon
, Joshua A. Broussard
, Jennifer L. Koetsier
, Lisa M. Godsel
Gillian N. Fitz
, Margaret L. Gardel
& Kathleen J. Green
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, high-
lighting its morphogenetic potential.
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago 60611 IL, USA.
Department of Dermatology, Northwestern
University Feinberg School of Medicine, Chicago 60611 IL, USA.
Institute for Biophysical Dynamics, University of Chicago, Chicago 60637 IL, USA.
Correspondence and requests for materials should be addressed to K.J.G. (email: firstname.lastname@example.org)