Letter abstract
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 elegans
Assunta 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 Fiore1,2,7
Redundant 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.
- IFOM Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
- Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milan, Italy.
- ABI/Molecular Neurogenetics, LMU, Schillerstrasse 44, Munich, 80336 Munich, Germany.
- Department of Experimental Medicine, Anatomy Section, University of Genova, Via de Toni 14, 16132 Genova, Italy.
- Dynamique du Cytosquelette Laboratoire d'Enzymologie et Biochimie Structurales, C. N.R.S., 91198 Gif-sur Yvette, France.
- BioIII/Bioinformatics and Molecular Genetics, Schanzlerstrasse 1, 79104 Freiburg, Germany.
- Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, Via di Rudini' 8, 20122 Milan, Italy.
Correspondence to: Pier Paolo Di Fiore1,2,7 e-mail: pierpaolo.difiore@ifom-ieo-campus.it
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