RRC ID 46672
Author Silhankova M, Port F, Harterink M, Basler K, Korswagen HC.
Title Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells.
Journal EMBO J
Abstract 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.
Volume 29(24)
Pages 4094-105
Published 2010-12-15
DOI 10.1038/emboj.2010.278
PII emboj2010278
PMID 21076391
PMC PMC3018790
MeSH Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism* Drosophila / enzymology Gene Knockdown Techniques Gene Knockout Techniques Intracellular Signaling Peptides and Proteins Phosphatidylinositol Phosphates / metabolism Phosphoric Monoester Hydrolases Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism* Protein Tyrosine Phosphatases, Non-Receptor / genetics Protein Tyrosine Phosphatases, Non-Receptor / metabolism* Wnt Proteins / metabolism
IF 9.889
Times Cited 29
C.elegans tm1523