Myosin VI is required for E-cadherin-mediated border cell migration.
Myosin VI (MyoVI) is a pointed-end-directed, actin-based motor protein, and mutations in the gene result in disorganization of hair cell stereocilia and cause deafness in mice. MyoVI also localizes to the leading edges of growth-factor-stimulated fibroblast cells and has been suggested to be involved in cell motility. There has been no direct test of this hypothesis, however. Drosophila melanogaster MyoVI is expressed in a small group of migratory follicle cells, known as border cells. Here we show that depletion of MyoVI specifically from border cells severely inhibited their migration. Similar to MyoVI, E-cadherin is required for border cell migration. We found that E-cadherin and Armadillo (Arm, Drosophila beta-catenin) protein levels were specifically reduced in cells lacking MyoVI, whereas other proteins were not. In addition, MyoVI protein levels were reduced in cells lacking DE-cadherin or Arm. MyoVI and Arm co-immunoprecipitated from ovarian protein extracts. These data suggest that MyoVI is required for border cell migration where it stabilizes E-cadherin and Arm. Mutations in MyoVIIA, another unconventional myosin protein, also lead to deafness, and MyoVIIA interacts with E-cadherin through a membrane protein called vezatin. Multiple biochemical mechanisms may exist, therefore, for cadherins to associate with diverse unconventional myosins that are required for normal stereocilium formation or maintenance.
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Erika R
ER
Geisbrecht
Denise J
DJ
Montell
D000818:Animals; D030801:Animals, Genetically Modified; D051186:Armadillo Domain Proteins; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D005260:Female; D019476:Insect Proteins / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D051176:beta Catenin
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D020409:Molecular Motor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; C089785:myosin VI; D018995:Myosin Heavy Chains