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Updated: Jun 13, 2025

Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
A feedback loop between plakophilin 4 and YAP signaling regulates keratinocyte differentiation
Lisa Müller1,2, Tony Gutschner2, Mechthild Hatzfeld1
1Institute of Molecular Medicine, Section for Pathochemistry, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Research Center, Kurt-Mothes-Str. 3A, 06120 Halle, Germany.
Abstract:
The Hippo signaling pathway is an important regulator of organ growth and differentiation, and its deregulation contributes to the development of cancer. The activity of its downstream targets YAP/TAZ depends on adherens junctions. Plakophilin 4 (PKP4) is a cell-type specific adherens junction protein expressed in the proliferating cells of the epidermis. Here, we show that PKP4 diminishes proliferation as well as differentiation. Depletion of PKP4 increased proliferation but at the same time induced premature epidermal differentiation. PKP4 interacted with several Hippo pathway components, including the transcriptional co-activators YAP/TAZ, and promoted nuclear YAP localization and target gene expression. In differentiated keratinocytes, PKP4 recruited LATS and YAP to cell junctions where YAP is transcriptionally inactive. YAP depletion, on the other hand, reduced PKP4 levels and keratinocyte adhesion indicative of a feedback mechanism controlling adhesion, proliferation, and differentiation by balancing YAP functions.
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