Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation

Lyulcheva, E., Taylor, E., Michael, M., Vehlow, A., Tan, S., Fletcher, A., Krause, M. and Bennett, D. (2008) Drosophila pico and its mammalian ortholog lamellipodin activate serum response factor and promote cell proliferation. Developmental Cell, 15(5), pp. 680-690. (doi: 10.1016/j.devcel.2008.09.020) (PMID:19000833) (PMCID:PMC2691947)

Abstract

Summary 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.

• Item Type: Articles
• Additional Information: This work was supported by Cancer Research UK (grant C20691/A6678) to D.B., with additional support from the Biotechnology and Biological Sciences Research Council, the Wellcome Trust, and the Royal Society. Work in the laboratory of M.K. is supported by a Wellcome Trust University Award (grant 077429/Z/05/Z) and an Medical Research Council studentship. E.L. was funded by an Oxford University European Scatcherd Scholarship and a Phizackerley Senior Scholarship at Balliol College, Oxford. D.B. was Todd-Bird Research Fellow at New College, Oxford.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fletcher, Dr Adam
• Authors: Lyulcheva, E., Taylor, E., Michael, M., Vehlow, A., Tan, S., Fletcher, A., Krause, M., and Bennett, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Developmental Cell
• Publisher: Elsevier
• ISSN: 1534-5807
• ISSN (Online): 1878-1551
• Copyright Holders: Copyright © 2008 Elsevier Inc.
• First Published: First published in Development Cell 15(5):680-690
• Publisher Policy: Reproduced under a Creative Commons licence