Crk proteins transduce FGF signaling to promote lens fiber cell elongation
| Autor: | Tom Curran, Gen-Sheng Feng, Lin Chen, Xin Zhang, Lawrence A. Quilliam, Yingyu Mao, Hongge Li, Tamica N. Collins, Angela Hong, Michael Bouaziz, Tae-Ju Park, Fen Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mouse Protein Tyrosine Phosphatase Non-Receptor Type 11 Fibroblast growth factor Biochemistry Mice Adapter molecule crk Morphogenesis FGF Biology (General) General Neuroscience Nuclear Proteins General Medicine Proto-Oncogene Proteins c-crk Lens Fiber Cell biology medicine.anatomical_structure Lens (anatomy) embryonic structures Medicine Stem cell Research Article Protein Binding Signal Transduction Cell type Cells--Morphology animal structures QH301-705.5 Science Biology General Biochemistry Genetics and Molecular Biology cell shape 03 medical and health sciences Biochemistry and Chemical Biology Lens Crystalline Developmental biology medicine Grb2 Animals Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Retina General Immunology and Microbiology Frs2 Fibroblasts CRKL Fibroblast growth factors Developmental Biology and Stem Cells 030104 developmental biology Shp2 Ras |
| Zdroj: | eLife, Vol 7 (2018) eLife |
| Popis: | 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. eLife digest As an embryo develops, its cells divide multiple times to transform into the specialized cell types that form our tissues and organs. To carry out specific roles, cells need to be of a certain shape. For example, in mammals, the cells that make up the main portion of the eye lens, develop into a fiber-like shape to be perfectly aligned with each other. This enables them to transmit light to the retina at the rear end of the eye. To do so, the lens cells increase over 1000 times in length with the help of a group of proteins called the Fibroblast Growth Factor, or FGF for short. The FGF pathway includes a network of interacting proteins that transmit signals to molecules inside the lens cells to control how they specialize and grow. However, until now it was not clear how it does this. Here, Zhang et al. used mouse lens-cells grown in the laboratory to investigate how FGF signaling causes cells to change their structure. The experiments revealed two related proteins called Crk and Crkl that linked the FGF pathway with another signaling system. When these two proteins were removed from the lens cells, the lens cells were still able to specialize, but could no longer grow in length. This suggests that these two processes are independent of each other. Moreover, Crk and Crkl helped the cells to change shape by increasing the amount of another group of proteins called Ras, which are known to both help cells to specialize and to regulate their shape. Zhang et al. discovered that the amount of Ras proteins determined whether cells specialized or modified their shape by changing the organization of proteins in the cell. Millions of children are born with cataracts, a disease caused when lens cells fail to shape properly. A better knowledge of FGF signaling may help to understand how cataracts develop and inspire future treatments. Moreover, the pathways identified in this study could also apply to other organs and diseases in which FGF signaling is active. |
| Databáze: | OpenAIRE |
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