Abstract
Ena/VASP family proteins are important modulators of cell migration and localize to focal adhesions, stress fibres and the very tips of lamellipodia and filopodia. Proline-rich proteins like vinculin and zyxin are well established interaction partners, which mediate Ena/VASP-recruitment via their EVH1-domains to focal adhesions and stress fibres. However, it is still unclear, which binding partners Ena/VASP proteins may have at lamellipodia tips and how their recruitment to these cellular protrusions is regulated. Here, we report the identification of a novel protein with high similarity to the C. elegans MIG-10 protein, which we termed PREL1 (Proline Rich EVH1 Ligand). PREL1 is a 74 kDa protein and shares homology with the Grb7-family of signalling adaptors. We show that PREL1 directly binds to Ena/VASP proteins and co-localizes with them at lamellipodia tips and at focal adhesions in response to Ras activation. Moreover, PREL1 directly binds to activated Ras in a phosphoinositide-dependent manner. Thus, our data pinpoint PREL1 as the first direct link between Ras signalling and cytoskeletal remodelling via Ena/VASP proteins during cell migration and spreading.
Publication types
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Duplicate Publication
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / immunology
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Actin Cytoskeleton / metabolism*
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Actins / metabolism
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Adaptor Proteins, Signal Transducing / analysis
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Adaptor Proteins, Signal Transducing / immunology
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Antibodies, Monoclonal / immunology
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Biological Assay
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Cell Adhesion
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Cell Adhesion Molecules / metabolism*
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Cell Line
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Cell Movement / physiology
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Cytoskeletal Proteins
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism*
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Fibroblasts / chemistry
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Fibronectins / chemistry
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Glycoproteins / immunology
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Humans
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Immunoprecipitation
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Membrane Proteins
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Mice
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Microfilament Proteins / metabolism*
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Phosphoproteins / metabolism*
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Pseudopodia / chemistry
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Pseudopodia / physiology
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Signal Transduction
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Vinculin / immunology
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Zyxin
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ras Proteins / metabolism*
Substances
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APBB1IP protein, human
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Actins
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Adaptor Proteins, Signal Transducing
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Antibodies, Monoclonal
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Cell Adhesion Molecules
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Cytoskeletal Proteins
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DNA-Binding Proteins
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ENA-VASP proteins
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Fibronectins
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Glycoproteins
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Membrane Proteins
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Microfilament Proteins
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Phosphoproteins
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ZYX protein, human
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Zyxin
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vasodilator-stimulated phosphoprotein
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Vinculin
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ras Proteins