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.
Geisbrecht
Erika R
ER
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Montell
Denise J
DJ
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