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.
A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegans / A. Croce, G. Cassata, A. Disanza, M.C. Gagliani, C. Tacchetti, M.G. Malabarba, M.F. Carlier, G. Scita, R. Baumeister, P.P. Di Fiore. - In: NATURE CELL BIOLOGY. - ISSN 1465-7392. - 6:12(2004 Dec), pp. 1173-1179.
|Titolo:||A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegans|
|Parole Chiave:||Animals; Caenorhabditis elegans Proteins; Organogenesis; Carrier Proteins; Sequence Homology, Nucleic Acid; Protein Isoforms; DNA, Complementary; Microscopy, Electron, Transmission; Epithelial Cells; Intestines; Adaptor Proteins, Signal Transducing; Caenorhabditis elegans; Molecular Sequence Data; Actins; Proteins; Cytoskeletal Proteins; Microvilli; Sequence Homology, Amino Acid; Protein Structure, Tertiary; Actin Cytoskeleton|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||dic-2004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/ncb1198|
|Appare nelle tipologie:||01 - Articolo su periodico|