Nature Cell Biology
6, 1173 - 1179 (2004)
Published online: 21 November 2004; | doi:10.1038/ncb1198
A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegansAssunta Croce1, 2, Giuseppe Cassata1, 3, Andrea Disanza1, 2, Maria Cristina Gagliani4, Carlo Tacchetti4, Maria Grazia Malabarba1, 2, Marie-France Carlier5, Giorgio Scita1, 2, Ralf Baumeister3, 6
& Pier Paolo Di Fiore1, 2, 71
IFOM Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy. 2
Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milan, Italy. 3
ABI/Molecular Neurogenetics, LMU, Schillerstrasse 44, Munich, 80336 Munich, Germany. 4
Department of Experimental Medicine, Anatomy Section, University of Genova, Via de Toni 14, 16132 Genova, Italy. 5
Dynamique du Cytosquelette Laboratoire d'Enzymologie et Biochimie Structurales, C. N.R.S., 91198 Gif-sur Yvette, France. 6
BioIII/Bioinformatics and Molecular Genetics, Schanzlerstrasse 1, 79104 Freiburg, Germany. 7
Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, Via di Rudini' 8, 20122 Milan, Italy.
Correspondence should be addressed to Pier Paolo Di Fiore pierpaolo.difiore@ifom-ieo-campus.itRedundant gene function frequently hampers investigations of the physiological roles of mammalian proteins. This is the case for Eps8, a receptor tyrosine kinase (RTK) substrate1 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 phenotype2, owing to the redundant function of three other EPS8-related genes6. 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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