Crim1 regulates integrin signaling in murine lens developmentстатья из журнала
Аннотация: The developing lens constitutes a powerful system for investigating the molecular basis of inductive tissue interactions and for studying cataract, the leading cause of blindness. The formation of tightly controlled cell-cell adhesions and cell-matrix junctions between lens epithelial (LE) cells, between lens fiber (LF) cells, and between these two cell populations enables the vertebrate lens to adopt its highly ordered structure and to acquire its optical transparency. Adhesion molecules are thought to maintain this ordered structure, but little is known about their identity or molecular interactions. Cysteine-rich motor neuron 1 (CRIM1), a type I transmembrane protein, is strongly expressed in the developing lens and its mutation causes ocular disease in both mice and humans. However, how Crim1 regulates lens morphogenesis is not understood. We identified a novel ENU-induced hypomorphic allele of Crim1, Crim1glcr11, which in the homozygous state causes cataract and microphthalmia. Using this allele and two other Crim1 mutant alleles, Crim1null and Crim1cko, we show that the lens defects in Crim1 mutants originate from defective LE cell polarity, proliferation and cell adhesion. The Crim1 adhesive function is likely required for interactions both between LE cells and between LE and LF cells. We further show that Crim1 acts in LE cells where it co-localizes with and regulates the levels of active β1 integrin and of phosphorylated FAK and ERK (pFAK, pERK). Lastly, the RGD and transmembrane motifs of Crim1 are required for the regulation of pFAK. These results identify an important function for Crim1 in the regulation of integrin- and FAK-mediated LE cell adhesion during lens development.
Год издания: 2015
Авторы: Ying Zhang, Jieqing Fan, Joshua W. K. Ho, Tommy Hu, Stephen C. Kneeland, Xueping Fan, Qiongchao Xi, Michael A. Sellarole, Wilhelmine N. de Vries, Lu W, Salil A. Lachke, Richard A. Lang, Simon W. M. John, Richard L. Maas
Издательство: The Company of Biologists
Источник: Development
Ключевые слова: Connexins and lens biology, Intraocular Surgery and Lenses, Protease and Inhibitor Mechanisms
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