The Wnt/PCP formin Daam1 drives cell-cell adhesion during nephron development

Cell Rep. 2021 Jul 6;36(1):109340. doi: 10.1016/j.celrep.2021.109340.

Abstract

E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development and homeostasis of epithelial tissues. 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 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 contacts in the developing nephron. Furthermore, analyses of junctional filamentous actin (F-actin) upon Daam1 depletion indicate decreased microfilament localization and slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional E-cadherin, mediated by Daam1's formin homology domain 2 (FH2). Finally, we establish that Daam1 signaling promotes organized movement of renal cells. This study demonstrates that Daam1 formin junctional activity is critical for epithelial tissue organization.

Keywords: Daam1; E-cadherin; F-actin; Wnt; Xenopus; adhesion; formin; kidney; nephron; tubulogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cadherins / metabolism
  • Cell Adhesion
  • Dogs
  • Embryo, Nonmammalian / metabolism
  • Embryo, Nonmammalian / ultrastructure
  • Female
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Imaging, Three-Dimensional
  • Madin Darby Canine Kidney Cells
  • Male
  • Nephrons / embryology*
  • Nephrons / metabolism*
  • Nephrons / ultrastructure
  • Protein Domains
  • Protein Transport
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Daam1 protein, Xenopus
  • Xenopus Proteins
  • Green Fluorescent Proteins