Crk proteins transduce FGF signaling to promote lens fiber cell elongation

• DOI: 10.7554/elife.32586
• Publication Date: 2018-01-23T13:00:29Z
• Authors: Tamica N Collins; Yingyu Mao; Hongge Li; Michael Bouaziz; Angela Hong; Gen-Sheng Feng; Fen Wang; Lawrence A Quilliam; Lin Chen; Taeju Park; Tom Curran; Xin Zhang
• Keywords: 0301 basic medicine; 570; Cells--Morphology; QH301-705.5; Science; 610; chemical biology; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Non-Receptor Type 11; Biochemistry; cell shape; developmental biology; Lens; Mice; 03 medical and health sciences; stem cells; Biochemistry and Chemical Biology; Lens, Crystalline; Developmental biology; Grb2; Morphogenesis; biochemistry; FGF; Animals; Biology (General); Cell Shape; mouse; Adaptor Proteins, Signal Transducing; GRB2 Adaptor Protein; 0303 health sciences; Crystalline; Q; Signal Transducing; Frs2; R; Adaptor Proteins; Nuclear Proteins; Fibroblasts; Proto-Oncogene Proteins c-crk; Fibroblast Growth Factors; Fibroblast growth factors; Medicine; Shp2; Protein Tyrosine Phosphatase; Ras; Protein Binding; Signal Transduction

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.