Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 312 (5775): 921-924

Copyright © 2006 by the American Association for the Advancement of Science

Wnt Gradient Formation Requires Retromer Function in Wnt-Producing Cells

Damien Y. M. Coudreuse, Giulietta Roël,* Marco C. Betist,* Olivier Destrée, Hendrik C. Korswagen{dagger}

Abstract: Wnt proteins function as morphogens that can form long-range concentration gradients to pattern developing tissues. Here, we show that the retromer, a multiprotein complex involved in intracellular protein trafficking, is required for long-range signaling of the Caenorhabditis elegans Wnt ortholog EGL-20. The retromer functions in EGL-20–producing cells to allow the formation of an EGL-20 gradient along the anteroposterior axis. This function is evolutionarily conserved, because Wnt target gene expression is also impaired in the absence of the retromer complex in vertebrates. These results demonstrate that the ability of Wnt to regulate long-range patterning events is dependent on a critical and conserved function of the retromer complex within Wnt-producing cells.

Hubrecht Laboratory and Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, Netherlands.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: rkors{at}

Microscale technologies for regulating human stem cell differentiation.
E. Cimetta and G. Vunjak-Novakovic (2014)
Experimental Biology and Medicine
   Abstract »    Full Text »    PDF »
The regulation and deregulation of Wnt signaling by PARK genes in health and disease.
D. C. Berwick and K. Harvey (2014)
J Mol Cell Biol 6, 3-12
   Abstract »    Full Text »    PDF »
FGF signaling regulates Wnt ligand expression to control vulval cell lineage polarity in C. elegans.
P. J. Minor, T.-F. He, C. H. Sohn, A. R. Asthagiri, and P. W. Sternberg (2013)
Development 140, 3882-3891
   Abstract »    Full Text »    PDF »
Wnt Proteins.
K. Willert and R. Nusse (2012)
Cold Spring Harb Perspect Biol 4, a007864
   Abstract »    Full Text »    PDF »
{beta}-Catenin-Dependent Wnt Signaling in C. elegans: Teaching an Old Dog a New Trick.
B. M. Jackson and D. M. Eisenmann (2012)
Cold Spring Harb Perspect Biol 4, a007948
   Abstract »    Full Text »    PDF »
UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit.
J. Schneider, R. L. Skelton, S. E. Von Stetina, T. C. Middelkoop, A. van Oudenaarden, H. C. Korswagen, and D. M. Miller III (2012)
Development 139, 2234-2245
   Abstract »    Full Text »    PDF »
WNTs in synapse formation and neuronal circuitry.
M. Park and K. Shen (2012)
EMBO J. 31, 2697-2704
   Abstract »    Full Text »    PDF »
Loss of Porcupine impairs convergent extension during gastrulation in zebrafish.
Q. Chen, R. Takada, and S. Takada (2012)
J. Cell Sci. 125, 2224-2234
   Abstract »    Full Text »    PDF »
Inhibition of Retromer Activity by Herpesvirus Saimiri Tip Leads to CD4 Downregulation and Efficient T Cell Transformation.
D. Kingston, H. Chang, A. Ensser, H.-R. Lee, J. Lee, S.-H. Lee, J. U. Jung, and N.-H. Cho (2011)
J. Virol. 85, 10627-10638
   Abstract »    Full Text »    PDF »
Regulation of developmental intercellular signalling by intracellular trafficking.
B.-Z. Shilo and E. D. Schejter (2011)
EMBO J. 30, 3516-3526
   Abstract »    Full Text »    PDF »
Neuroblast migration along the anteroposterior axis of C. elegans is controlled by opposing gradients of Wnts and a secreted Frizzled-related protein.
M. Harterink, D. h. Kim, T. C. Middelkoop, T. D. Doan, A. van Oudenaarden, and H. C. Korswagen (2011)
Development 138, 2915-2924
   Abstract »    Full Text »    PDF »
Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells.
M. Silhankova, F. Port, M. Harterink, K. Basler, and H. C. Korswagen (2010)
EMBO J. 29, 4094-4105
   Abstract »    Full Text »    PDF »
Analyses of SORTING NEXINs Reveal Distinct Retromer-Subcomplex Functions in Development and Protein Sorting in Arabidopsis thaliana.
M. Pourcher, M. Santambrogio, N. Thazar, A.-M. Thierry, I. Fobis-Loisy, C. Miege, Y. Jaillais, and T. Gaude (2010)
PLANT CELL 22, 3980-3991
   Abstract »    Full Text »    PDF »
FIP1/RCP Binding to Golgin-97 Regulates Retrograde Transport from Recycling Endosomes to the trans-Golgi Network.
J. Jing, J. R. Junutula, C. Wu, J. Burden, H. Matern, A. A. Peden, and R. Prekeris (2010)
Mol. Biol. Cell 21, 3041-3053
   Abstract »    Full Text »    PDF »
Retromer Is Required for Apoptotic Cell Clearance by Phagocytic Receptor Recycling.
D. Chen, H. Xiao, K. Zhang, B. Wang, Z. Gao, Y. Jian, X. Qi, J. Sun, L. Miao, and C. Yang (2010)
Science 327, 1261-1264
   Abstract »    Full Text »    PDF »
Xenopus Wntless and the Retromer Complex Cooperate To Regulate XWnt4 Secretion.
H. Kim, S.-M. Cheong, J. Ryu, H.-J. Jung, E.-h. Jho, and J.-K. Han (2009)
Mol. Cell. Biol. 29, 2118-2128
   Abstract »    Full Text »    PDF »
Wnt Signaling and Stem Cell Control.
R. Nusse, C. Fuerer, W. Ching, K. Harnish, C. Logan, A. Zeng, D. ten Berge, and Y. Kalani (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Regulation of Wnt protein secretion and its role in gradient formation.
K. Bartscherer and M. Boutros (2008)
EMBO Rep. 9, 977-982
   Abstract »    Full Text »    PDF »
Complex Network of Wnt Signaling Regulates Neuronal Migrations During Caenorhabditis elegans Development.
A. Y. Zinovyeva, Y. Yamamoto, H. Sawa, and W. C. Forrester (2008)
Genetics 179, 1357-1371
   Abstract »    Full Text »    PDF »
{beta}-Catenin asymmetry is regulated by PLA1 and retrograde traffic in C. elegans stem cell divisions.
T. Kanamori, T. Inoue, T. Sakamoto, K. Gengyo-Ando, M. Tsujimoto, S. Mitani, H. Sawa, J. Aoki, and H. Arai (2008)
EMBO J. 27, 1647-1657
   Abstract »    Full Text »    PDF »
An in Vivo Map of the Yeast Protein Interactome.
K. Tarassov, V. Messier, C. R. Landry, S. Radinovic, M. M. S. Molina, I. Shames, Y. Malitskaya, J. Vogel, H. Bussey, and S. W. Michnick (2008)
Science 320, 1465-1470
   Abstract »    Full Text »    PDF »
Arabidopsis VPS35, a Retromer Component, is Required for Vacuolar Protein Sorting and Involved in Plant Growth and Leaf Senescence.
M. Yamazaki, T. Shimada, H. Takahashi, K. Tamura, M. Kondo, M. Nishimura, and I. Hara-Nishimura (2008)
Plant Cell Physiol. 49, 142-156
   Abstract »    Full Text »    PDF »
Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation.
V. I. Korolchuk, M. M. Schutz, C. Gomez-Llorente, J. Rocha, N. R. Lansu, S. M. Collins, Y. P. Wairkar, I. M. Robinson, and C. J. O'Kane (2007)
J. Cell Sci. 120, 4367-4376
   Abstract »    Full Text »    PDF »
The C. elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway.
J. L. Green, T. Inoue, and P. W. Sternberg (2007)
Development 134, 4053-4062
   Abstract »    Full Text »    PDF »
WNTers in La Jolla.
S. Y. Sokol and K. A. Wharton Jr (2007)
Development 134, 3393-3399
   Abstract »    Full Text »    PDF »
Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube.
L. M. Galli, T. L. Barnes, S. S. Secrest, T. Kadowaki, and L. W. Burrus (2007)
Development 134, 3339-3348
   Abstract »    Full Text »    PDF »
Grd19/Snx3p functions as a cargo-specific adapter for retromer-dependent endocytic recycling.
T. I. Strochlic, T. G. Setty, A. Sitaram, and C. G. Burd (2007)
J. Cell Biol. 177, 115-125
   Abstract »    Full Text »    PDF »
The canonical Wnt signalling pathway and its APC partner in colon cancer development.
J. Schneikert and J. Behrens (2007)
Gut 56, 417-425
   Full Text »    PDF »
The making of Wnt: new insights into Wnt maturation, sorting and secretion.
D. Coudreuse and H. C. Korswagen (2007)
Development 134, 3-12
   Full Text »    PDF »
A WNTer wonderland in Snowbird..
X. He and J. D. Axelrod (2006)
Development 133, 2597-2603
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882