Crk proteins transduce FGF signaling to promote lens fiber cell elongation
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 cytos...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32586 |
| _version_ | 1811236857448497152 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tamica N Collins |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:15:17Z |
| format | Article |
| id | doaj.art-103552b2bf844c2ab53e6ef5980e37ed |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:15:17Z |
| publishDate | 2018-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-103552b2bf844c2ab53e6ef5980e37ed2022-12-22T03:33:26ZengeLife Sciences Publications LtdeLife2050-084X2018-01-01710.7554/eLife.32586Crk proteins transduce FGF signaling to promote lens fiber cell elongationTamica N Collins0Yingyu Mao1Hongge Li2Michael Bouaziz3Angela Hong4Gen-Sheng Feng5Fen Wang6Lawrence A Quilliam7Lin Chen8Taeju Park9Tom Curran10Xin Zhang11https://orcid.org/0000-0001-5555-0825Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United StatesDepartments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United StatesDepartments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United StatesDepartments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United StatesDepartments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United StatesDepartment of Pathology, University of California San Diego, La Jolla, United StatesCenter for Cancer Biology and Nutrition, Houston, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Rehabilitation Medicine, Third Military Medical University, Chongqing, ChinaThe Children's Research Institute, Children's Mercy Kansas City, Kansas City, United StatesThe Children's Research Institute, Children's Mercy Kansas City, Kansas City, United StatesDepartments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, United StatesSpecific 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.https://elifesciences.org/articles/32586FGFFrs2Shp2Grb2Rascell shape |
| spellingShingle | 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 Crk proteins transduce FGF signaling to promote lens fiber cell elongation eLife FGF Frs2 Shp2 Grb2 Ras cell shape |
| title | Crk proteins transduce FGF signaling to promote lens fiber cell elongation |
| title_full | Crk proteins transduce FGF signaling to promote lens fiber cell elongation |
| title_fullStr | Crk proteins transduce FGF signaling to promote lens fiber cell elongation |
| title_full_unstemmed | Crk proteins transduce FGF signaling to promote lens fiber cell elongation |
| title_short | Crk proteins transduce FGF signaling to promote lens fiber cell elongation |
| title_sort | crk proteins transduce fgf signaling to promote lens fiber cell elongation |
| topic | FGF Frs2 Shp2 Grb2 Ras cell shape |
| url | https://elifesciences.org/articles/32586 |
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