Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells

Dev Cell. 2008 Jan;14(1):140-7. doi: 10.1016/j.devcel.2007.12.004. Epub 2007 Dec 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Line
  • Cell Membrane / physiology
  • Endosomes / physiology
  • Golgi Apparatus / physiology
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Kidney
  • Recombinant Proteins / metabolism
  • Transfection
  • Wnt Proteins / genetics
  • Wnt Proteins / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Mig-14 protein, C elegans
  • Recombinant Proteins
  • Wnt Proteins