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

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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.

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  1. 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 to: Pier Paolo Di Fiore1,2,7 e-mail: pierpaolo.difiore@ifom-ieo-campus.it



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