Wnt Signaling Requires Retromer-Dependent Recycling of MIG-14/Wntless in Wnt-Producing Cells

• Published in: Developmental cell Vol. 14; no. 1; pp. 140 - 147
• Main Authors: Yang, Pei-Tzu, Lorenowicz, Magdalena J., Silhankova, Marie, Coudreuse, Damien Y.M., Betist, Marco C., Korswagen, Hendrik C.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.01.2008; Cell Press
• Subjects: Animals; Biological and medical sciences; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - physiology; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell Membrane - physiology; Cell physiology; CELLBIO; Endosomes - physiology; Fundamental and applied biological sciences. Psychology; Golgi Apparatus - physiology; HeLa Cells; Humans; Kidney; Molecular and cellular biology; Recombinant Proteins - metabolism; Signal transduction; SIGNALING; Transfection; Wnt Proteins - genetics; Wnt Proteins - physiology; CELLBIO; SIGNALING; Development; Signal transduction; Cell signaling
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2007.12.004

Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. We have previously shown that Wnt signaling requires retromer function in Wnt-producing cells. The retromer is a multiprotein complex that mediates endosome-to-Golgi transport of specific sorting receptors. MIG-14/Wls is a conserved transmembrane protein that binds Wnt and is required in Wnt-producing cells for Wnt secretion. Here, we demonstrate that in the absence of retromer function, MIG-14/Wls is degraded in lysosomes and becomes limiting for Wnt signaling. We show that retromer-dependent recycling of MIG-14/Wls is part of a trafficking pathway that retrieves MIG-14/Wls from the plasma membrane. We propose that MIG-14/Wls cycles between the Golgi and the plasma membrane to mediate Wnt secretion. Regulation of this transport pathway may enable Wnt-producing cells to control the range of Wnt signaling in the tissue.