Crk proteins transduce FGF signaling to promote lens fiber cell elongation

Elife. 2018 Jan 23;7:e32586. doi: 10.7554/eLife.32586.

Abstract

Specific cell shapes are fundamental to the organization and function of multicellular organisms. Fibroblast Growth Factor (FGF) signaling induces the elongation of lens fiber cells during vertebrate lens development. Nonetheless, exactly how this extracellular FGF signal is transmitted to the cytoskeletal network has previously not been determined. Here, we show that the Crk family of adaptor proteins, Crk and Crkl, are required for mouse lens morphogenesis but not differentiation. Genetic ablation and epistasis experiments demonstrated that Crk and Crkl play overlapping roles downstream of FGF signaling in order to regulate lens fiber cell elongation. Upon FGF stimulation, Crk proteins were found to interact with Frs2, Shp2 and Grb2. The loss of Crk proteins was partially compensated for by the activation of Ras and Rac signaling. These results reveal that Crk proteins are important partners of the Frs2/Shp2/Grb2 complex in mediating FGF signaling, specifically promoting cell shape changes.

Keywords: FGF; Frs2; Grb2; Ras; Shp2; biochemistry; cell shape; chemical biology; developmental biology; mouse; stem cells.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Shape*
  • Fibroblast Growth Factors / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / physiology*
  • GRB2 Adaptor Protein / metabolism
  • Lens, Crystalline / embryology*
  • Mice
  • Morphogenesis
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
  • Proto-Oncogene Proteins c-crk / metabolism*
  • Signal Transduction*

Substances

  • Adaptor Proteins, Signal Transducing
  • CRKL protein
  • Crk protein, mouse
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-crk
  • Fibroblast Growth Factors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Ptpn11 protein, mouse