α-parvin is required for epidermal morphogenesis, hair follicle development and basal keratinocyte polarity

PLoS One. 2020 Mar 12;15(3):e0230380. doi: 10.1371/journal.pone.0230380. eCollection 2020.

Abstract

Epidermal morphogenesis and hair follicle (HF) development depend on the ability of keratinocytes to adhere to the basement membrane (BM) and migrate along the extracellular matrix. Integrins are cell-matrix receptors that control keratinocyte adhesion and migration, and are recognized as major regulators of epidermal homeostasis. How integrins regulate the behavior of keratinocytes during epidermal morphogenesis remains insufficiently understood. Here, we show that α-parvin (α-pv), a focal adhesion protein that couples integrins to actin cytoskeleton, is indispensable for epidermal morphogenesis and HF development. Inactivation of the murine α-pv gene in basal keratinocytes results in keratinocyte-BM detachment, epidermal thickening, ectopic keratinocyte proliferation and altered actin cytoskeleton polarization. In vitro, α-pv-null keratinocytes display reduced adhesion to BM matrix components, aberrant spreading and stress fibers formation, and impaired directed migration. Together, our data demonstrate that α-pv controls epidermal homeostasis by facilitating integrin-mediated adhesion and actin cytoskeleton organization in keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Basement Membrane / cytology
  • Basement Membrane / metabolism*
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Epidermis / growth & development*
  • Focal Adhesions / metabolism
  • Hair Follicle / metabolism*
  • Integrins / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins / physiology*
  • Morphogenesis / physiology*

Substances

  • Actins
  • Integrins
  • Microfilament Proteins
  • Parva protein, mouse

Grants and funding

This work was funded by the Max Planck Society and the DFG (MO-2562/1-2).