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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / metabolism
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Actin Cytoskeleton / ultrastructure
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Actins / biosynthesis*
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Adaptor Proteins, Signal Transducing
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Animals
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Caenorhabditis elegans / embryology*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / isolation & purification
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Caenorhabditis elegans Proteins / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism*
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Cytoskeletal Proteins
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Epithelial Cells / metabolism
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Epithelial Cells / ultrastructure
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Intestinal Mucosa / metabolism
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Intestines / embryology*
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Intestines / ultrastructure
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Microscopy, Electron, Transmission
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Microvilli / metabolism
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Microvilli / ultrastructure
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Molecular Sequence Data
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Organogenesis / physiology*
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary / genetics
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Proteins / genetics
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cytoskeletal Proteins
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DNA, Complementary
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EPS-8 protein, C elegans
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Eps8 protein, mouse
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Protein Isoforms
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Proteins
Associated data
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GENBANK/AY611484
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GENBANK/AY611485