Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells.
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.
Yang
Pei-Tzu
PT
Hubrecht Institute, Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Lorenowicz
Magdalena J
MJ
Silhankova
Marie
M
Coudreuse
Damien Y M
DY
Betist
Marco C
MC
Korswagen
Hendrik C
HC
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D011992:Endosomes / Q000502:physiology; D006056:Golgi Apparatus / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527888:Mig-14 protein, C elegans; D011994:Recombinant Proteins; D051153:Wnt Proteins