TY - JOUR
T1 - A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion
AU - Harterink, M.
AU - Port, F.
AU - Lorenowicz, M.J.
AU - McGough, I.J.
AU - Silhankova, M.
AU - Betist, M.C.
AU - van Weering, J.R.
AU - van Heesbeen, R.G.
AU - Middelkoop, T.C.
AU - Basler, K.
AU - Cullen, P.J.
AU - Korswagen, H.C.
N1 - Reporting year: 2011
PY - 2011
Y1 - 2011
N2 - Wnt proteins are lipid-modified glycoproteins that play a central role in development, adult tissue homeostasis and disease. Secretion of Wnt proteins is mediated by the Wnt-binding protein Wntless (Wls), which transports Wnt from the Golgi network to the cell surface for release. It has recently been shown that recycling of Wls through a retromer-dependent endosome-to-Golgi trafficking pathway is required for efficient Wnt secretion, but the mechanism of this retrograde transport pathway is poorly understood. Here, we report that Wls recycling is mediated through a retromer pathway that is independent of the retromer sorting nexins SNX1-SNX2 and SNX5-SNX6. We have found that the unrelated sorting nexin, SNX3, has an evolutionarily conserved function in Wls recycling and Wnt secretion and show that SNX3 interacts directly with the cargo-selective subcomplex of the retromer to sort Wls into a morphologically distinct retrieval pathway. These results demonstrate that SNX3 is part of an alternative retromer pathway that functionally separates the retrograde transport of Wls from other retromer cargo. [KEYWORDS: Animals, Animals, Genetically Modified, Biological Transport, Active, Caenorhabditis elegans/genetics/growth & development/metabolism, Drosophila/genetics/growth & development/metabolism, Endosomes/metabolism, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins/ metabolism, Models, Biological, RNA Interference, Signal Transduction, Sorting Nexins/antagonists & inhibitors/genetics/ metabolism, Wnt Proteins/ metabolism, trans-Golgi Network/metabolism]
AB - Wnt proteins are lipid-modified glycoproteins that play a central role in development, adult tissue homeostasis and disease. Secretion of Wnt proteins is mediated by the Wnt-binding protein Wntless (Wls), which transports Wnt from the Golgi network to the cell surface for release. It has recently been shown that recycling of Wls through a retromer-dependent endosome-to-Golgi trafficking pathway is required for efficient Wnt secretion, but the mechanism of this retrograde transport pathway is poorly understood. Here, we report that Wls recycling is mediated through a retromer pathway that is independent of the retromer sorting nexins SNX1-SNX2 and SNX5-SNX6. We have found that the unrelated sorting nexin, SNX3, has an evolutionarily conserved function in Wls recycling and Wnt secretion and show that SNX3 interacts directly with the cargo-selective subcomplex of the retromer to sort Wls into a morphologically distinct retrieval pathway. These results demonstrate that SNX3 is part of an alternative retromer pathway that functionally separates the retrograde transport of Wls from other retromer cargo. [KEYWORDS: Animals, Animals, Genetically Modified, Biological Transport, Active, Caenorhabditis elegans/genetics/growth & development/metabolism, Drosophila/genetics/growth & development/metabolism, Endosomes/metabolism, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins/ metabolism, Models, Biological, RNA Interference, Signal Transduction, Sorting Nexins/antagonists & inhibitors/genetics/ metabolism, Wnt Proteins/ metabolism, trans-Golgi Network/metabolism]
U2 - 10.1038/ncb2281
DO - 10.1038/ncb2281
M3 - Article
SN - 1465-7392
VL - 13
SP - 914
EP - 923
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 8
ER -