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Crk proteins transduce FGF signaling to promote lens fiber cell elongation

Collins, Tamica; Mao, Yingyu; Li, Hongge; Bouaziz, Michael; Hong, Angela; Feng, Gen-Sheng; Wang, Fen; Quilliam, Lawrence A.; Chen, Lin; Park, Taeju; Curran, Tom; Zhang, Xin

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.

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Academic Units
Ophthalmology
Pathology and Cell Biology
Published Here
August 11, 2018