Present address: Department of Cell Biology, Faculty of Science, Charles University Prague, Vinicna 7, 128 00 Prague 2, Czech Republic
Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells
Version of Record online: 12 NOV 2010
Copyright © 2010 European Molecular Biology Organization
The EMBO Journal
Volume 29, Issue 24, pages 4094–4105, December 15, 2010
How to Cite
Silhankova, M., Port, F., Harterink, M., Basler, K. and Korswagen, H. C. (2010), Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells. The EMBO Journal, 29: 4094–4105. doi: 10.1038/emboj.2010.278
There is a Have you seen? (August 2011) associated with this Article.
- Issue online: 15 DEC 2010
- Version of Record online: 12 NOV 2010
- Manuscript Accepted: 19 OCT 2010
- Manuscript Received: 6 JUL 2010
- C. elegans;
Wnt proteins are lipid-modified glycoproteins that have important roles in development, adult tissue homeostasis and disease. Secretion of Wnt proteins from producing cells is mediated by the Wnt-binding protein MIG-14/Wls, which binds Wnt in the Golgi network and transports it to the cell surface for release. It has recently been shown that recycling of MIG-14/Wls from the plasma membrane to the trans-Golgi network is required for efficient Wnt secretion, but the mechanism of this retrograde transport pathway is still poorly understood. In this study, we report the identification of MTM-6 and MTM-9 as novel regulators of MIG-14/Wls trafficking in Caenorhabditis elegans. MTM-6 and MTM-9 are myotubularin lipid phosphatases that function as a complex to dephosphorylate phosphatidylinositol-3-phosphate, a central regulator of endosomal trafficking. We show that mutation of mtm-6 or mtm-9 leads to defects in several Wnt-dependent processes and demonstrate that MTM-6 is required in Wnt-producing cells as part of the MIG-14/Wls-recycling pathway. This function is evolutionarily conserved, as the MTM-6 orthologue DMtm6 is required for Wls stability and Wg secretion in Drosophila. We conclude that regulation of endosomal trafficking by the MTM-6/MTM-9 myotubularin complex is required for the retromer-dependent recycling of MIG-14/Wls and Wnt secretion.