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

Abstract

Myosin X (Myo X), also known as MYO10, is an unconventional actin-based motor protein that plays an important role in filopodium formation. Its intra-filopodia movement, an event tightly associated with the function of Myo X, has been extensively studied. However, how the motor activity of Myo X and the direction of its movements are regulated remains largely unknown. In our previous study, we demonstrated that DCC (for 'deleted in colorectal carcinoma') and neogenin (neogenin 1, NEO1 or NGN), a family of immunoglobin-domain-containing transmembrane receptors for netrins, interact with Myo X and that DCC is a cargo of Myo X to be delivered to the neurites of cultured neurons. Here, we provide evidence for DCC and neogenin as regulators of Myo X. DCC promotes movement of Myo X along basal actin filaments and enhances Myo-X-mediated basal filopodium elongation. By contrast, neogenin appears to suppress Myo X movement on the basal side, but increases its movement towards the apical and dorsal side of a cell, promoting dorsal filopodium formation and growth. Further studies have demonstrated that DCC, but not neogenin, enhances integrin-mediated tyrosine phosphorylation of focal adhesion kinase and basal F-actin reorganization, providing a cellular mechanism underlying their distinct effects on Myo X. These results thus demonstrate differential regulatory roles on Myo X activity by its cargo proteins, DCC and neogenin, revealing different cellular functions of DCC and neogenin.

• Authors: Yu Liu, Yun Peng, Peng-Gao Dai, Quan-Sheng Du, Lin Mei, Wen-Cheng Xiong
• Journal: Journal of cell science (J Cell Sci) Vol. 125 Issue Pt 3 Pg. 751-62 (Feb 01 2012) ISSN: 1477-9137 [Electronic] England
• PMID: 22349703 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Actins
• DCC Receptor
• Dcc protein, mouse
• Membrane Proteins
• Myo10 protein, mouse
• Receptors, Cell Surface
• Recombinant Fusion Proteins
• Tumor Suppressor Proteins
• neogenin
• Green Fluorescent Proteins
• Myosins

Topics

• Actins (metabolism)
• Animals
• Cell Compartmentation
• Cell Line
• Cell Movement (physiology)
• DCC Receptor
• Green Fluorescent Proteins (genetics, metabolism)
• Membrane Proteins (genetics, metabolism)
• Mice
• Models, Biological
• Myosins (genetics, metabolism)
• Neurons (physiology)
• Protein Transport
• Pseudopodia (physiology)
• Receptors, Cell Surface (genetics, metabolism)
• Recombinant Fusion Proteins (genetics, metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)