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Wnt signalling requires MTM‐6 and MTM‐9 myotubularin lipid‐phosphatase function in Wnt‐producing cells
Author(s) -
Silhankova Marie,
Port Fillip,
Harterink Martin,
Basler Konrad,
Korswagen Hendrik C
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.278
Subject(s) - biology , wnt signaling pathway , phosphatase , microbiology and biotechnology , function (biology) , signalling , biochemistry , signal transduction , phosphorylation
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.