Crk proteins transduce FGF signaling to promote lens fiber cell elongation

• Published in: eLife Vol. 7
• Main Authors: Collins, Tamica N, Mao, Yingyu, Li, Hongge, Bouaziz, Michael, Hong, Angela, Feng, Gen-Sheng, Wang, Fen, Quilliam, Lawrence A, Chen, Lin, Park, Taeju, Curran, Tom, Zhang, Xin
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 23.01.2018; eLife Sciences Publications, Ltd
• Subjects: Ablation; Adaptor proteins; Adaptor Proteins, Signal Transducing - metabolism; Animals; Biochemistry and Chemical Biology; Biology; Biotechnology; Cell adhesion & migration; Cell growth; Cell Shape; Cell size; Cytoskeleton; Developmental Biology; Elongation; Epistasis; FGF; Fibroblast growth factors; Fibroblast Growth Factors - metabolism; Fibroblasts - drug effects; Fibroblasts - physiology; Frs2; Glycerol; Grb2; GRB2 Adaptor Protein - metabolism; Grb2 protein; Kinases; Lens, Crystalline - embryology; Measurement techniques; Mice; Morphogenesis; Nuclear Proteins - metabolism; Phosphorylation; Protein Binding; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism; Proteins; Proto-Oncogene Proteins c-crk - metabolism; Ras; Shp2; Signal Transduction; United States > US; Shp2; mouse; stem cells; FGF; chemical biology; Ras; cell shape; developmental biology; biochemistry; Frs2; Grb2
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.32586

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 and 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.