Myosin X regulates netrin receptors and functions in axonal path-finding

  title={Myosin X regulates netrin receptors and functions in axonal path-finding},
  author={Xiao-Juan Zhu and Cheng-zhong Wang and Peng Dai and Yi Xie and Ning-Ning Song and Yu Liu and Quan-sheng Du and Lin Mei and Yu-Qiang Ding and Wen-Cheng Xiong},
  journal={Nature Cell Biology},
Netrins regulate axon path-finding during development, but the underlying mechanisms are not well understood. Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites… 

Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development

Netrin-1 increases Myosin X (Myo X) interaction with KIF13B, and thus promotes axonal delivery of Myo X and axon initiation and contralateral branching in developing cerebral neurons, revealing unrecognized functions and mechanisms underlying Netrin- 1 regulation of axon development.

Differential regulation of myosin X movements by its cargos, DCC and neogenin

Different regulatory roles on Myo X activity by its cargo proteins, DCC and neogenin are demonstrated, revealing different cellular functions of D CC and neogensin.

p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance*

A novel mechanism is provided that exploits the scaffolding properties of the N terminus of p120RasGAP to tightly regulate netrin-1/DCC-dependent axon outgrowth and guidance in embryonic cortical neurons.

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.

Myo10 is required for neurogenic cell adhesion and migration

It is found that knockdown of endogenous Myo10 in a normal gonadotropin-releasing hormone (GnRH) neuronal cell line transfected with the large T antigen (NLT) induced the impairment of cell motility and orientation, and N-cadherin, a calcium-dependent classical cell adhesion molecule, rescued the migration deficiency caused by Myo 10 knockdown in cell aggregates and collagen gel assay.

Myosin X and its motorless isoform differentially modulate dendritic spine development by regulating trafficking and retention of vasodilator-stimulated phosphoprotein

This study demonstrates a novel biological function for Hdl-Myo10 and an important new role for both Myo10 isoforms in the development of dendritic spines and synapses in hippocampal neurons.

Myosin X regulates neuronal radial migration through interacting with N-cadherin

A novel mechanism of Myo10 interacting with N-cadherin and regulating its cell-surface expression, which is required for neuronal adhesion and migration is revealed.

PtdIns (3,4,5) P3 Recruitment of Myo10 Is Essential for Axon Development

Mechanism studies demonstrated that the recruitment of Myo10 through its PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns) P3 was essential for axon formation and in vivo studies confirmed that Myo 10 was required for neuronal morphological transition during radial neuronal migration in the developmental neocortex.

Emerging roles for neogenin and its ligands in CNS development

Neogenin is a multifunctional receptor regulating diverse developmental processes, and its contribution to neural development is proving to be considerably more extensive than originally predicted.

Myo10 is a key regulator of TNT formation in neuronal cells

Results indicate that, in neuronal cells, TNTs can arise from a subset of Myo10-driven dorsal filopodia, independent of its binding to integrins and N-cadherins.



Phosphatidylinositol transfer protein-α in netrin-1-induced PLC signalling and neurite outgrowth

Evidence for a role of phosphatidylinositol transfer protein-α (PITPα) in neurite extension in response to netrin-1, an extracellular guidance cue is provided, revealing a signalling mechanism for DCC/neogenin and PITPα regulation.

Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation

It is shown that Dcc activates mitogen-activated protein kinase (MAPK) signalling, by means of extracellular signal-regulated kinases (ERK)-1 and -2, on netrin-1 binding in both transfected cells and commissural neurons, which contributes to netrin signalling in axon growth and guidance.

Myo10 in brain: developmental regulation, identification of a headless isoform and dynamics in neurons

It is reported here that, in addition to full-length Myo10, brain expresses a shorter form of MyO10 that lacks a myosin head domain, which is unable to function as a molecular motor and, like it, contains three pleckstrin homology (PH) domains.

DCC-dependent Phospholipase C Signaling in Netrin-1-induced Neurite Elongation*

Evidence that netrin-1 stimulates phosphatidylinositol bisphosphate hydrolysis in cortical neurons is provided and a crucial role of PLC signaling is demonstrated in netin-1-induced neurite elongation in cortex.

Focal adhesion kinase in netrin-1 signaling

It is reported that the netrin receptor DCC (deleted in colorectal cancer) interacts with the focal adhesion kinase (FAK), a kinase implicated in regulating cell adhesion and migration, and this results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin -1 function.

Myosin-X provides a motor-based link between integrins and the cytoskeleton

Results indicate that Myo10-mediated relocalization of integrins might serve to form adhesive structures and thereby promote filopodial extension.

Activation of FAK and Src are receptor-proximal events required for netrin signaling

A model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling is suggested.

The Netrin 1 Receptors Unc5h3 and Dcc Are Necessary at Multiple Choice Points for the Guidance of Corticospinal Tract Axons

It is demonstrated that the Unc5h3 gene product, shown previously to regulate cerebellar granule cell migrations, also controls the guidance of the corticospinal tract, the major tract responsible for coordination of limb movements, and confirms that both the cellular and axonal guidance functions of C. elegans unc-5 have been conserved in vertebrates.