title: Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation.
abstract: MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog, pico, is required for tissue and organismal growth. Reduction in pico levels resulted in reduced cell division rates, growth retardation, increased G:F actin ratios and lethality. Conversely, pico overexpression reduced G:F actin ratios and promoted tissue overgrowth in an epidermal growth factor (EGF) receptor (EGFR)-dependent manner. Consistently, in HeLa cells, lamellipodin was required for EGF-induced proliferation. We show that pico and lamellipodin share the ability to activate serum response factor (SRF), a transcription factor that responds to reduced G:F-actin ratios via its co-factor Mal. Genetics data indicate that mal/SRF levels are important for pico-mediated tissue growth. We propose that MRL proteins link EGFR activation to mitogenic SRF signaling via changes in actin dynamics.
authors.affiliation: Department of Zoology, Oxford University, South Parks Road, Oxford OX1 3PS, UK.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Lyulcheva
authors.forename: Eleanor
authors.initials: E
authors.lastname: Taylor
authors.forename: Magdalene
authors.initials: M
authors.lastname: Michael
authors.forename: Anne
authors.initials: A
authors.lastname: Vehlow
authors.forename: Shengjiang
authors.initials: S
authors.lastname: Tan
authors.forename: Adam
authors.initials: A
authors.lastname: Fletcher
authors.forename: Matthias
authors.initials: M
authors.lastname: Krause
authors.forename: Daimark
authors.initials: D
authors.lastname: Bennett
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C092744:ENA-VASP proteins; D008565:Membrane Proteins; C533183:Pico protein, Drosophila; C493339:RAPH1 protein, human; D026362:Serum Response Factor; D066246:ErbB Receptors