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bioRxiv · 10.1101/2020.08.18.256123

Cell-Cell Adhesion During Nephron Development Is Driven by Wnt/PCP Formin Daam1

Miller, R. K.·Krneta-Stankic, V.·Corkins, M. E.·Kloc, M.·Gladden, A. B.·Paulucci-Holthauzen, A.
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Abstract

E-cadherin junctions facilitate the assembly and disassembly of cell-cell contacts that drive development and homeostasis of epithelial tissues. The stability of E-cadherin-based junctions highly depends on their attachment to the actin cytoskeleton, but little is known about how the assembly of junctional actin filaments is regulated. Formins are a conserved group of proteins responsible for the formation and elongation of filamentous actin (F-actin). In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/ planar cell polarity (PCP) formin protein Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin based intercellular adhesion. Using live imaging we show that Daam1 localizes to newly formed cell-cell contacts in the developing nephron. Furthermore, analyses of junctional F-actin upon Daam1 depletion indicate a decrease in microfilament localization and their slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional E-cadherin, which is mediated by Daam1s formin homology domain 2 (FH2). Finally, we establish that Daam1 signaling is essential for promoting organized movement of renal cells. This study demonstrates that Daam1 formin junctional activity is critical for epithelial tissue organization.

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Miller, R. K., Krneta-Stankic, V., Corkins, M. E., Kloc, M., Gladden, A. B., Paulucci-Holthauzen, A.. 2020-08-19. Cell-Cell Adhesion During Nephron Development Is Driven by Wnt/PCP Formin Daam1. https://doi.org/10.1101/2020.08.18.256123

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