title: Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration.
abstract: BACKGROUND
  Cell migration is essential during development and in human disease progression including cancer. Most cell migration studies concentrate on known or predicted components of migration pathways.
  
  
  RESULTS
  Here we use data from a genome-wide RNAi morphology screen in Drosophila melanogaster cells together with bioinformatics to identify 26 new regulators of morphology and cytoskeletal organization in human cells. These include genes previously implicated in a wide range of functions, from mental retardation, Down syndrome and Huntington's disease to RNA and DNA-binding genes. We classify these genes into seven groups according to phenotype and identify those that affect cell migration. We further characterize a subset of seven genes, FAM40A, FAM40B, ARC, FMNL3, FNBP3/FBP11, LIMD1 and ZRANB1, each of which has a different effect on cell shape, actin filament distribution and cell migration. Interestingly, in several instances closely related isoforms with a single Drosophila homologue have distinct phenotypes. For example, FAM40B depletion induces cell elongation and tail retraction defects, whereas FAM40A depletion reduces cell spreading.
  
  
  CONCLUSIONS
  Our results identify multiple regulators of cell migration and cytoskeletal signalling that are highly conserved between Drosophila and humans, and show that closely related paralogues can have very different functions in these processes.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE11UL, UK.
authors.forename: Siau Wei
authors.initials: SW
authors.lastname: Bai
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Herrera-Abreu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rohn
authors.forename: Victor
authors.initials: V
authors.lastname: Racine
authors.forename: Virginia
authors.initials: V
authors.lastname: Tajadura
authors.forename: Narendra
authors.initials: N
authors.lastname: Suryavanshi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bechtel
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiemann
authors.forename: Buzz
authors.initials: B
authors.lastname: Baum
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D048430:Cell Shape / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology; D017344:Genes, Insect / Q000235:genetics; D005820:Genetic Testing; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D011506:Proteins; D034741:RNA, Small Interfering