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

TY - JOUR

T1 - Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells.

AU - Yang, P.T.

AU - Lorenowicz, M.J.

AU - Silhankova, M.

AU - Coudreuse, D.Y.M.

AU - Betist, M.C.

AU - Korswagen, H.C.

N1 - Reporting year: 2008

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1016/j.devcel.2007.12.004

DO - 10.1016/j.devcel.2007.12.004

M3 - Article

SN - 1534-5807

VL - 14

SP - 140

EP - 147

JO - Developmental Cell

JF - Developmental Cell

IS - 1

ER -