# MYO10

## Overview
MYO10 is a gene that encodes the unconventional myosin motor protein, myosin X. This protein is distinguished by its unique structural features, including a motor domain for ATP hydrolysis and actin binding, and a tail region with pleckstrin homology (PH), MyTH4, and FERM domains. These domains facilitate its interactions with cellular membranes and other proteins, playing a critical role in intracellular transport and cell motility (Berg2002MyosinX; Bohil2006MyosinX). Myosin X is particularly involved in the formation and function of filopodia, which are actin-rich protrusions that aid in cell movement, adhesion, and environmental sensing (Bohil2006MyosinX). The protein's ability to form dimers and its interactions with various cellular components underscore its importance in processes such as epithelial morphogenesis, spindle orientation, and signal transduction (Quintero2012Myosin; Liu2012MyosinX). Additionally, MYO10 has been implicated in several developmental disorders and diseases, including cancer and infectious diseases, highlighting its significance in both normal physiology and pathological conditions (Courson2015MyosinX; Heimsath2017MyosinX).

## Structure
MYO10, or myosin X, is an unconventional myosin protein characterized by a complex molecular structure that facilitates its role in intracellular transport and cell motility. The protein includes a motor domain responsible for ATP hydrolysis and actin binding, which is essential for its motility and localization to filopodial tips (Berg2002MyosinX). The neck region contains three IQ motifs that bind calmodulin light chains, contributing to its structural stability and function (Bohil2006MyosinX).

The tail region of MYO10 is particularly notable for its unique composition, including pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM domain. These domains are involved in signaling and binding to transmembrane proteins, playing a crucial role in MYO10's ability to interact with cellular membranes and other proteins (Berg2002MyosinX). The MyTH4 domain is critical for filopodia formation, as its deletion impairs this function (Bohil2006MyosinX).

MYO10 can form antiparallel coiled-coil dimers, which are essential for its processive walking mechanism along actin filaments. This dimerization is crucial for its function in filopodia formation and is dependent on the full-length structure of the protein (Quintero2012Myosin). The protein also undergoes post-translational modifications, such as phosphorylation, which may regulate its activity and interactions. Multiple splice variants of MYO10 exist, contributing to its functional diversity (Bohil2006MyosinX).

## Function
MYO10 (myosin X) is a molecular motor protein that plays a critical role in the formation of filopodia, which are slender, actin-rich protrusions on the surface of cells. These structures are essential for cell motility, adhesion, and environmental sensing. MYO10 localizes to the tips of filopodia and is involved in their formation by promoting the assembly and stabilization of actin filaments. It acts downstream of the small GTPase Cdc42, a key regulator of filopodia, and can induce filopodia formation independently of VASP proteins (Bohil2006MyosinX).

In polarized epithelial cells, MYO10 is crucial for maintaining the paracellular barrier and is involved in epithelial morphogenesis. It localizes to the basolateral domain and is implicated in junction formation and spindle orientation during cell division. Knockdown of MYO10 results in increased paracellular permeability and defects in lumen formation, indicating its role in maintaining epithelial cell structure and function (Liu2012MyosinX).

MYO10's unique structure, including its MyTH4 and FERM domains, allows it to interact with integrins and other components at the filopodial tips, suggesting a role in transporting or anchoring molecules necessary for filopodial dynamics (Berg2002MyosinX; Bohil2006MyosinX).

## Clinical Significance
Mutations and alterations in the MYO10 gene have been linked to several developmental and disease conditions. In mice, MYO10 knockout results in a range of developmental abnormalities, including exencephaly, a severe neural tube defect, and persistent hyaloid vasculature, which can lead to ocular defects such as microphthalmia and anophthalmia (Heimsath2017MyosinX). These findings suggest that MYO10 is crucial for neural tube closure, pigmentation, and eye development, and its dysfunction may contribute to similar conditions in humans (Heimsath2017MyosinX).

MYO10 is also implicated in cancer progression. It plays a role in the formation of filopodia and invadopodia, structures that facilitate cancer cell invasion and metastasis. Alterations in MYO10 expression, regulated by pathways such as PI3 kinase and EGR1, can lead to more aggressive cancer phenotypes (Courson2015MyosinX). In glioblastomas, MYO10 is overexpressed, supporting tumor malignancy, and its knockout impairs tumor growth, indicating its potential role in tumor development (Nurminen2024Previously).

In infectious diseases, MYO10 is important for the replication and spread of pathogens like Ebola and Marburg viruses, as well as bacterial infections such as Shigella flexneri, highlighting its role in infectious disease processes (Courson2015MyosinX).

## Interactions
MYO10 (myosin X) is involved in various protein interactions that are crucial for its function in cellular processes. It interacts with the BMP receptor ALK6, facilitating the transport of ALK6 to filopodia, which is essential for BMP6 signaling in endothelial cells. This interaction is important for coordinating filopodial function and BMP signaling during endothelial cell migration and angiogenesis (Pi2007Sequential).

Myo10 also interacts with the spindle assembly factor TPX2 via its MyTH4/FERM domain, which is crucial for recruiting or maintaining TPX2 at the spindle pole during mitosis. This interaction is essential for spindle pole integrity and function (Woolner2008Myosin10).

In neuronal cells, Myo10 interacts with netrin receptors, specifically deleted in colorectal cancer (DCC) and neogenin (NEO1). DCC has a greater binding affinity for full-length Myo10, while neogenin associates more strongly with the headless form of Myo10. These interactions are significant for the formation of tunneling nanotubes (TNTs) and the spread of prion particles (Gousset2013Myo10).

Myo10's FERM domain is involved in binding to integrins, which are important for cell adhesion and signaling. This interaction is relevant to its function in spindle pole biology and potentially in other cellular processes (Yim2023Myosin).


## References


[1. (Berg2002MyosinX) Jonathan S. Berg and Richard E. Cheney. Myosin-x is an unconventional myosin that undergoes intrafilopodial motility. Nature Cell Biology, 4(3):246–250, February 2002. URL: http://dx.doi.org/10.1038/ncb762, doi:10.1038/ncb762. This article has 318 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1038/ncb762)

[2. (Quintero2012Myosin) Omar A. Quintero and Christopher M. Yengo. Myosin x dimerization and its impact on cellular functions. Proceedings of the National Academy of Sciences, 109(43):17313–17314, October 2012. URL: http://dx.doi.org/10.1073/pnas.1216035109, doi:10.1073/pnas.1216035109. This article has 4 citations.](https://doi.org/10.1073/pnas.1216035109)

[3. (Heimsath2017MyosinX) Ernest G. Heimsath, Yang-In Yim, Mirna Mustapha, John A. Hammer, and Richard E. Cheney. Myosin-x knockout is semi-lethal and demonstrates that myosin-x functions in neural tube closure, pigmentation, hyaloid vasculature regression, and filopodia formation. Scientific Reports, December 2017. URL: http://dx.doi.org/10.1038/s41598-017-17638-x, doi:10.1038/s41598-017-17638-x. This article has 54 citations and is from a peer-reviewed journal.](https://doi.org/10.1038/s41598-017-17638-x)

4. (Yim2023Myosin) Myosin 10 uses its MyTH4 and FERM domains differentially to support two aspects of spindle pole biology required for mitotic spindle bipolarity. This article has 0 citations.

[5. (Courson2015MyosinX) David S. Courson and Richard E. Cheney. Myosin-x and disease. Experimental Cell Research, 334(1):10–15, May 2015. URL: http://dx.doi.org/10.1016/j.yexcr.2015.03.014, doi:10.1016/j.yexcr.2015.03.014. This article has 40 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.yexcr.2015.03.014)

[6. (Liu2012MyosinX) Katy C. Liu, Damon T. Jacobs, Brian D. Dunn, Alan S. Fanning, and Richard E. Cheney. Myosin-x functions in polarized epithelial cells. Molecular Biology of the Cell, 23(9):1675–1687, May 2012. URL: http://dx.doi.org/10.1091/mbc.e11-04-0358, doi:10.1091/mbc.e11-04-0358. This article has 37 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1091/mbc.e11-04-0358)

[7. (Bohil2006MyosinX) Aparna B. Bohil, Brian W. Robertson, and Richard E. Cheney. Myosin-x is a molecular motor that functions in filopodia formation. Proceedings of the National Academy of Sciences, 103(33):12411–12416, August 2006. URL: http://dx.doi.org/10.1073/pnas.0602443103, doi:10.1073/pnas.0602443103. This article has 284 citations.](https://doi.org/10.1073/pnas.0602443103)

[8. (Gousset2013Myo10) Karine Gousset, Ludovica Marzo, Pierre-Henri Commere, and Chiara Zurzolo. Myo10 is a key regulator of tnt formation in neuronal cells. Journal of Cell Science, 126(19):4424–4435, October 2013. URL: http://dx.doi.org/10.1242/jcs.129239, doi:10.1242/jcs.129239. This article has 139 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1242/jcs.129239)

[9. (Pi2007Sequential) Xinchun Pi, Rongqin Ren, Russell Kelley, Chunlian Zhang, Martin Moser, Aparna B. Bohil, Melinda DiVito, Richard E. Cheney, and Cam Patterson. Sequential roles for myosin-x in bmp6-dependent filopodial extension, migration, and activation of bmp receptors. The Journal of Cell Biology, 179(7):1569–1582, December 2007. URL: http://dx.doi.org/10.1083/jcb.200704010, doi:10.1083/jcb.200704010. This article has 95 citations.](https://doi.org/10.1083/jcb.200704010)

[10. (Woolner2008Myosin10) Sarah Woolner, Lori L. O’Brien, Christiane Wiese, and William M. Bement. Myosin-10 and actin filaments are essential for mitotic spindle function. The Journal of Cell Biology, 182(1):77–88, July 2008. URL: http://dx.doi.org/10.1083/jcb.200804062, doi:10.1083/jcb.200804062. This article has 187 citations.](https://doi.org/10.1083/jcb.200804062)

[11. (Nurminen2024Previously) Riikka Nurminen, Ebrahim Afyounian, Niina Paunu, Riku Katainen, Mari Isomäki, Anssi Nurminen, Mauro Scaravilli, Jenni Tolppanen, Vidal Fey, Anni Kivinen, Pauli Helén, Niko Välimäki, Juha Kesseli, Lauri A. Aaltonen, Hannu Haapasalo, Matti Nykter, and Kirsi J. Rautajoki. Previously reported ccdc26 risk variant and novel germline variants in galnt13, ar, and myo10 associated with familial glioma in finland. Scientific Reports, May 2024. URL: http://dx.doi.org/10.1038/s41598-024-62296-5, doi:10.1038/s41598-024-62296-5. This article has 0 citations and is from a peer-reviewed journal.](https://doi.org/10.1038/s41598-024-62296-5)