Myosin-X: a MyTH-FERM myosin at the tips of filopodia

@article{Kerber2011MyosinXAM,
  title={Myosin-X: a MyTH-FERM myosin at the tips of filopodia},
  author={Michael L. Kerber and Richard E. Cheney},
  journal={Journal of Cell Science},
  year={2011},
  volume={124},
  pages={3733 - 3741}
}
Myosin-X (Myo10) is an unconventional myosin with MyTH4-FERM domains that is best known for its striking localization to the tips of filopodia and its ability to induce filopodia. Although the head domain of Myo10 enables it to function as an actin-based motor, its tail contains binding sites for several molecules with central roles in cell biology, including phosphatidylinositol (3,4,5)-trisphosphate, microtubules and integrins. Myo10 also undergoes fascinating long-range movements within… 

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MyTH4-FERM myosins have an ancient and conserved role in filopod formation

The essential functional features of the DdMyo7 myosin were identified using quantitative live-cell imaging to characterize the ability of various mutants to rescue filopod formation in the myo7-null mutant, supporting fundamental functional conservation between these two distant myosins.

Myosin X.

  • H. Tokuo
  • Biology
    Advances in experimental medicine and biology
  • 2020
This chapter addresses the structure of the Myo10 gene; the molecular structure of Myosin X protein with its multiple domains; the regulation of actin structures induced in cells by Myo 10; the expression and function of Myo12 in vitro and in vivo; and the role of MyO10 in cancer.

Activated full-length myosin-X moves processively on filopodia with large steps toward diverse two-dimensional directions

Results suggest that the lever-arm of full-length myosin-X is flexible enough to processively steps on different actin filaments within the actin bundles of filopodia.

Optimized filopodia formation requires myosin tail domain cooperation

Weak dimerization activity of the DdMyo7 proximal tail allows for sensitive regulation of myosin activity to prevent inappropriate activation of filopodia formation, revealing that the principles of MF myOSin-based filopODia formation are conserved via divergent mechanisms for dimerized.

Myosin X dimerization and its impact on cellular functions

An antiparallel dimerization mechanism in myosin X (MYO10) is demonstrated and it is suggested that this structural arrangement allows more efficient processive walking in the parallel actin bundles of filopodia.

Myosin MyTH4-FERM structures highlight important principles of convergent evolution

Significance Myosins containing MyTH4-FERM (myosin tail homology 4-band 4.1, ezrin, radixin, moesin, or MF) domains in their tails are found in a wide range of phylogenetically divergent organisms, such as humans and the social amoeba Dictyostelium, suggesting common properties such as autoinhibition of the motor and microtubule binding to arise through convergent evolution.

The myosin X motor is optimized for movement on actin bundles

The model and kinetic data explain why large steps and high velocities can only occur on bundled filaments and why myosin X functions as an antiparallel dimer in cells with a unique geometry optimized for movement on actin bundles.

Myosin X and Cytoskeletal Reorganization

It is anticipated that the structural, biochemical and cell biological understanding of the binding partner dependent regulation of myosin X function can uncover the role of myOSin X in diverse cell biological processes and diseases.

Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation

Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation and proposed the following mechanism.

Myosin-X and disease.

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