A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegans

Assunta Croce, Giuseppe Cassata, Andrea Disanza, Maria Cristina Gagliani, Carlo Tacchetti, Maria Gracia Malabarba, Marie France Carlier, Giorgio Scita, Ralf Baumeister, Pier Paolo Di Fiore

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1173-1179
Number of pages7
JournalNature Cell Biology
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2004

ASJC Scopus subject areas

  • Cell Biology

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    Croce, A., Cassata, G., Disanza, A., Gagliani, M. C., Tacchetti, C., Malabarba, M. G., Carlier, M. F., Scita, G., Baumeister, R., & Di Fiore, P. P. (2004). A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegans. Nature Cell Biology, 6(12), 1173-1179. https://doi.org/10.1038/ncb1198