Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 May 15;334(1):10-5.
doi: 10.1016/j.yexcr.2015.03.014. Epub 2015 Mar 27.

Myosin-X and disease

David S Courson  1 , Richard E Cheney  2
Affiliations
Review

Myosin-X and disease

David S Courson et al. Exp Cell Res. .

Abstract

Myosin-X (Myo10) is a motor protein best known for its role in filopodia formation. New research implicates Myo10 in a number of disease states including cancer metastasis and pathogen infection. This review focuses on these developments with emphasis on the emerging roles of Myo10 in formation of cancer cell protrusions and metastasis. A number of aggressive cancers show high levels of Myo10 expression and knockdown of Myo10 has been shown to dramatically limit cancer cell motility in 2D and 3D systems. Myo10 knockdown also limits spread of intracellular pathogens marburgvirus and Shigella flexneri. Consideration is given to how these properties might arise and potential paths of future research.

Keywords: Cancer; Filopodia; Infectious disease; Metastasis; Myo10; Myosin-X.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(A) Bar diagram of Myo10. The bar diagram highlights the domains of the Myo10 heavy chain. It has a head domain containing the motor, a neck domain containing three IQ motifs, and a tail domain containing numerous binding domains. The region containing 3 PH domains binds PIP3. The MyTH4-FERM domain is response for binding to microtubules and integrins. (B) Hypothetical models of Myo10 structure based on structure of individual domains. Myo10 monomers can form a folded “off” state where the tail domain folds over onto the head domain. Binding to PIP3 allows the folded monomers to form active dimers. Dimeric myosins were previously thought to form parallel heavy chain dimers, but recent data indicates that Myo10 can form anti-parallel dimers.
Figure 2
Figure 2
Myo10 is hypothesized to be the molecular link between the actin cytoskeleton and integrin-based adhesions to the extra-cellular matrix in cellular protrusions like filopodia and cancer cell filopodium-like protrusions. Integrin patches have been observed in cellular protrusions. Myo10 is shown linking filopodial actin to integrin patches that engage with the extracellular matrix. Filopodial adhesion can form and release rapidly, so the relative simplicity of this model is appealing. Studies of cells expressing Myo10 mutants that lack integrin binding have shown decreased filopodial adhesion and migration, further corroborating this model.
See this image and copyright information in PMC

References

    1. Berg JS, Derfler BH, Pennisi CM, Corey DP, Cheney RE. Myosin-X, a novel myosin with pleckstrin homology domains, associates with regions of dynamic actin. J Cell Sci. 2000;113(Pt 19):3439–3451. - PubMed
    1. Berg JS, Cheney RE. Myosin-X is an unconventional myosin that undergoes intrafilopodial motility. Nat Cell Biol. 2002;4:246–250. - PubMed
    1. Mattila PK, Lappalainen P. Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol. 2008;9:446–454. - PubMed
    1. Svitkina TM, Bulanova EA, Chaga OY, Vignjevic DM, Kojima S, Vasiliev JM, Borisy GG. Mechanism of filopodia initiation by reorganization of a dendritic network. J Cell Biol. 2003;160:409–421. - PMC - PubMed
    1. Bohil AB, Robertson BW, Cheney RE. Myosin-X is a molecular motor that functions in filopodia formation. Proc Natl Acad Sci U S A. 2006;103:12411–12416. - PMC - PubMed

Publication types