TY - JOUR
T1 - A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegans
AU - Croce, Assunta
AU - Cassata, Giuseppe
AU - Disanza, Andrea
AU - Gagliani, Maria Cristina
AU - Tacchetti, Carlo
AU - Malabarba, Maria Gracia
AU - Carlier, Marie France
AU - Scita, Giorgio
AU - Baumeister, Ralf
AU - Di Fiore, Pier Paolo
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=10344222932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10344222932&partnerID=8YFLogxK
U2 - 10.1038/ncb1198
DO - 10.1038/ncb1198
M3 - Article
C2 - 15558032
AN - SCOPUS:10344222932
VL - 6
SP - 1173
EP - 1179
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 12
ER -