A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegans |
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Authors: | Croce Assunta Cassata Giuseppe Disanza Andrea Gagliani Maria Cristina Tacchetti Carlo Malabarba Maria Grazia Carlier Marie-France Scita Giorgio Baumeister Ralf Di Fiore Pier Paolo |
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Institution: | IFOM Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy. |
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Abstract: | Redundant gene function frequently hampers investigations of the physiological roles of mammalian proteins. This is the case for Eps8, a receptor tyrosine kinase (RTK) substrate that participates in the activation of the Rac-specific guanine nucleotide-exchange function of Sos1 (refs 2-5), thereby regulating actin remodelling by RTKs. EPS8-knockout mice, however, exhibit no evident phenotype, owing to the redundant function of three other EPS8-related genes. Here we show that in the nematode Caenorhabditis elegans, only one orthologue of the EPS8 gene exists, which gives rise to two alternatively spliced isoforms, EPS-8A and EPS-8B, differing at their carboxyl termini. In the nematode, eps-8 is essential for embryonic development. Furthermore, EPS-8A, but not EPS-8B, is specifically required for proper apical morphogenesis in the intestinal cells. This latter phenotype could be precisely correlated with a previously unknown actin barbed-end-capping activity, which is present in the C terminus of the EPS-8A isoform. Therefore, nematode genetics allowed not only the unmasking of distinct EPS-8-linked phenotypes, but also the definition of a novel function for this molecule in actin dynamics. |
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