論文 - 詳細
| RRC ID | 46672 |
|---|---|
| 著者 | Silhankova M, Port F, Harterink M, Basler K, Korswagen HC. |
| タイトル | Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells. |
| ジャーナル | 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. |
| 巻・号 | 29(24) |
| ページ | 4094-105 |
| 公開日 | 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 |
| 引用数 | 29 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 2 |
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| 線虫 | tm1523 |