PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins.
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.
Jenzora
Andrea
A
Department of Cell Biology, German Research Centre for Biotechnology (GBF), Braunschweig, Germany.
Behrendt
Barbara
B
Small
J Victor
JV
Wehland
Jürgen
J
Stradal
Theresia E B
TE
D008841:Actin Cytoskeleton / Q000276:immunology / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001681:Biological Assay; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D005347:Fibroblasts / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011554:Pseudopodia / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction; D016596:Vinculin / Q000276:immunology; D018631:ras Proteins / Q000378:metabolism*; D000098662:Vasodilator-Stimulated Phosphoprotein
C493340:APBB1IP protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005353:Fibronectins; D006023:Glycoproteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D016596:Vinculin; D018631:ras Proteins