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Myosin VI is required for E-cadherin-mediated border cell migration

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Abstract

Myosin VI (MyoVI) is a pointed-end-directed, actin-based motor protein1,2, and mutations in the gene result in disorganization of hair cell stereocilia and cause deafness in mice3. MyoVI also localizes to the leading edges of growth-factor-stimulated fibroblast cells4 and has been suggested to be involved in cell motility5. 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 β-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 vezatin6. Multiple biochemical mechanisms may exist, therefore, for cadherins to associate with diverse unconventional myosins that are required for normal stereocilium formation or maintenance.

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Figure 1: Myosin VI expression in the ovary.
Figure 2: Antisense depletion of MyoVI.
Figure 3: Expression of DE-cadherin and MyoVI in wild-type and mutant follicle cells.
Figure 4: Biochemical characterization of MyoVI interactions.

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Acknowledgements

We would like to acknowledge M. Bownes and K. Miller for MyoVI reagents and useful discussions. We thank M. Peifer for the Armadillo constructs. We thank C. Montell and members of the laboratory for critical reading of the manuscript. This work was supported by a grant from the National Institutes of Health, GM46425.

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Correspondence to Denise J. Montell.

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Geisbrecht, E., Montell, D. Myosin VI is required for E-cadherin-mediated border cell migration. Nat Cell Biol 4, 616–620 (2002). https://doi.org/10.1038/ncb830

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