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.

Science 31 August 2001:
Vol. 293. no. 5535, pp. 1663 - 1666
DOI: 10.1126/science.293.5535.1663
Prev | Table of Contents | Next

Reports

Regulation of Wnt Signaling and Embryo Patterning by an Extracellular Sulfatase

Gurtej K. Dhoot,1 Marcus K. Gustafsson,2 Xingbin Ai,2 Weitao Sun,2 David M. Standiford,2 Charles P. Emerson Jr.2*

The developmental signaling functions of cell surface heparan sulfate proteoglycans (HSPGs) are dependent on their sulfation states. Here, we report the identification of QSulf1, the avian ortholog of an evolutionarily conserved protein family related to heparan-specific N-acetyl glucosamine sulfatases. QSulf1 expression is induced by Sonic hedgehog in myogenic somite progenitors in quail embryos and is required for the activation of MyoD, a Wnt-induced regulator of muscle specification. QSulf1 is localized on the cell surface and regulates heparan-dependent Wnt signaling in C2C12 myogenic progenitor cells through a mechanism that requires its catalytic activity, providing evidence that QSulf1 regulates Wnt signaling through desulfation of cell surface HSPGs.

1 Department of Basic Veterinary Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 OTU, UK.
2 Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 1157 BRBII/III, 421 Curie Boulevard, Philadelphia, PA 19104-6058, USA
*   To whom correspondence should be addressed. E-mail: emersonc{at}mail.med.upenn.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Heparan Sulfate Proteoglycan Modulation of Wnt5A Signal Transduction in Metastatic Melanoma Cells.
M. P. O'Connell, J. L. Fiori, E. K. Kershner, B. P. Frank, F. E. Indig, D. D. Taub, K. S. Hoek, and A. T. Weeraratna (2009)
J. Biol. Chem. 284, 28704-28712
   Abstract »    Full Text »    PDF »
Characterization of the Human Sulfatase Sulf1 and Its High Affinity Heparin/Heparan Sulfate Interaction Domain.
M.-A. Frese, F. Milz, M. Dick, W. C. Lamanna, and T. Dierks (2009)
J. Biol. Chem. 284, 28033-28044
   Abstract »    Full Text »    PDF »
Functional Consequences of the Subdomain Organization of the Sulfs.
R. Tang and S. D. Rosen (2009)
J. Biol. Chem. 284, 21505-21514
   Abstract »    Full Text »    PDF »
Sulf Loss Influences N-, 2-O-, and 6-O-Sulfation of Multiple Heparan Sulfate Proteoglycans and Modulates Fibroblast Growth Factor Signaling.
W. C. Lamanna, M.-A. Frese, M. Balleininger, and T. Dierks (2008)
J. Biol. Chem. 283, 27724-27735
   Abstract »    Full Text »    PDF »
Transforming Growth Factor-{beta}1 Induces Heparan Sulfate 6-O-Endosulfatase 1 Expression in Vitro and in Vivo.
X. Yue, X. Li, H. T. Nguyen, D. R. Chin, D. E. Sullivan, and J. A. Lasky (2008)
J. Biol. Chem. 283, 20397-20407
   Abstract »    Full Text »    PDF »
Arylsulfatase G, a Novel Lysosomal Sulfatase.
M.-A. Frese, S. Schulz, and T. Dierks (2008)
J. Biol. Chem. 283, 11388-11395
   Abstract »    Full Text »    PDF »
6-O-Sulfation of Heparan Sulfate Differentially Regulates Various Fibroblast Growth Factor-dependent Signalings in Culture.
N. Sugaya, H. Habuchi, N. Nagai, S. Ashikari-Hada, and K. Kimata (2008)
J. Biol. Chem. 283, 10366-10376
   Abstract »    Full Text »    PDF »
Quail Sulf1 Function Requires Asparagine-linked Glycosylation.
R. K. Ambasta, X. Ai, and C. P. Emerson Jr. (2007)
J. Biol. Chem. 282, 34492-34499
   Abstract »    Full Text »    PDF »
SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation.
X. Ai, T. Kitazawa, A.-T. Do, M. Kusche-Gullberg, P. A. Labosky, and C. P. Emerson Jr (2007)
Development 134, 3327-3338
   Abstract »    Full Text »    PDF »
Essential Role of Heparan Sulfate 2-O-Sulfotransferase in Chick Limb Bud Patterning and Development.
T. Kobayashi, H. Habuchi, K. Tamura, H. Ide, and K. Kimata (2007)
J. Biol. Chem. 282, 19589-19597
   Abstract »    Full Text »    PDF »
Mice Deficient in Heparan Sulfate 6-O-Sulfotransferase-1 Exhibit Defective Heparan Sulfate Biosynthesis, Abnormal Placentation, and Late Embryonic Lethality.
H. Habuchi, N. Nagai, N. Sugaya, F. Atsumi, R. L. Stevens, and K. Kimata (2007)
J. Biol. Chem. 282, 15578-15588
   Abstract »    Full Text »    PDF »
Regulation of Heparan Sulfate 6-O-Sulfation by beta-Secretase Activity.
N. Nagai, H. Habuchi, S. Kitazume, H. Toyoda, Y. Hashimoto, and K. Kimata (2007)
J. Biol. Chem. 282, 14942-14951
   Abstract »    Full Text »    PDF »
Gene Trap Disruption of the Mouse Heparan Sulfate 6-O-Endosulfatase Gene, Sulf2.
D. H. Lum, J. Tan, S. D. Rosen, and Z. Werb (2007)
Mol. Cell. Biol. 27, 678-688
   Abstract »    Full Text »    PDF »
Genomewide Expression Profiling in the Zebrafish Embryo Identifies Target Genes Regulated by Hedgehog Signaling During Vertebrate Development.
J. Xu, B. P. Srinivas, S. Y. Tay, A. Mak, X. Yu, S. G. P. Lee, H. Yang, K. R. Govindarajan, B. Leong, G. Bourque, et al. (2006)
Genetics 174, 735-752
   Abstract »    Full Text »    PDF »
Specific and flexible roles of heparan sulfate modifications in Drosophila FGF signaling.
K. Kamimura, T. Koyama, H. Habuchi, R. Ueda, M. Masu, K. Kimata, and H. Nakato (2006)
J. Cell Biol. 174, 773-778
   Abstract »    Full Text »    PDF »
Molecular Profiling of Laser-Microdissected Matched Tumor and Normal Breast Tissue Identifies Karyopherin {alpha}2 as a Potential Novel Prognostic Marker in Breast Cancer..
E. Dahl, G. Kristiansen, K. Gottlob, I. Klaman, E. Ebner, B. Hinzmann, K. Hermann, C. Pilarsky, M. Durst, M. Klinkhammer-Schalke, et al. (2006)
Clin. Cancer Res. 12, 3950-3960
   Abstract »    Full Text »    PDF »
Mouse Cristin/R-spondin Family Proteins Are Novel Ligands for the Frizzled 8 and LRP6 Receptors and Activate beta-Catenin-dependent Gene Expression.
J.-S. Nam, T. J. Turcotte, P. F. Smith, S. Choi, and J. K. Yoon (2006)
J. Biol. Chem. 281, 13247-13257
   Abstract »    Full Text »    PDF »
Ventral neural progenitors switch toward an oligodendroglial fate in response to increased Sonic hedgehog (Shh) activity: involvement of Sulfatase 1 in modulating Shh signaling in the ventral spinal cord..
C. Danesin, E. Agius, N. Escalas, X. Ai, C. Emerson, P. Cochard, and C. Soula (2006)
J. Neurosci. 26, 5037-5048
   Abstract »    Full Text »    PDF »
Inhibition or Activation of Apert Syndrome FGFR2 (S252W) Signaling by Specific Glycosaminoglycans.
L. M. McDowell, B. A. Frazier, D. R. Studelska, K. Giljum, J. Chen, J. Liu, K. Yu, D. M. Ornitz, and L. Zhang (2006)
J. Biol. Chem. 281, 6924-6930
   Abstract »    Full Text »    PDF »
Overexpression of Heparan Sulfate 6-O-Sulfotransferases in Human Embryonic Kidney 293 Cells Results in Increased N-Acetylglucosaminyl 6-O-Sulfation.
A.-T. Do, E. Smeds, D. Spillmann, and M. Kusche-Gullberg (2006)
J. Biol. Chem. 281, 5348-5356
   Abstract »    Full Text »    PDF »
Substrate Specificity and Domain Functions of Extracellular Heparan Sulfate 6-O-Endosulfatases, QSulf1 and QSulf2.
X. Ai, A.-T. Do, M. Kusche-Gullberg, U. Lindahl, K. Lu, and C. P. Emerson Jr. (2006)
J. Biol. Chem. 281, 4969-4976
   Abstract »    Full Text »    PDF »
HSulf-1 and HSulf-2 Are Potent Inhibitors of Myeloma Tumor Growth in Vivo.
Y. Dai, Y. Yang, V. MacLeod, X. Yue, A. C. Rapraeger, Z. Shriver, G. Venkataraman, R. Sasisekharan, and R. D. Sanderson (2005)
J. Biol. Chem. 280, 40066-40073
   Abstract »    Full Text »    PDF »
Specific Structural Features of Heparan Sulfate Proteoglycans Potentiate Neuregulin-1 Signaling.
M. S. Pankonin, J. T. Gallagher, and J. A. Loeb (2005)
J. Biol. Chem. 280, 383-388
   Abstract »    Full Text »    PDF »
Functions of heparan sulfate proteoglycans in cell signaling during development.
X. Lin (2004)
Development 131, 6009-6021
   Abstract »    Full Text »    PDF »
Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging.
F. K. Johansson, J. Brodd, C. Eklof, M. Ferletta, G. Hesselager, C.-F. Tiger, L. Uhrbom, and B. Westermark (2004)
PNAS 101, 11334-11337
   Abstract »    Full Text »    PDF »
Abrogation of heparan sulfate synthesis in Drosophila disrupts the Wingless, Hedgehog and Decapentaplegic signaling pathways.
D. J. Bornemann, J. E. Duncan, W. Staatz, S. Selleck, and R. Warrior (2004)
Development 131, 1927-1938
   Abstract »    Full Text »    PDF »
QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis.
S. Wang, X. Ai, S. D. Freeman, M. E. Pownall, Q. Lu, D. S. Kessler, and C. P. Emerson Jr. (2004)
PNAS 101, 4833-4838
   Abstract »    Full Text »    PDF »
Domain-specific Modification of Heparan Sulfate by Qsulf1 Modulates the Binding of the Bone Morphogenetic Protein Antagonist Noggin.
B. L. Viviano, S. Paine-Saunders, N. Gasiunas, J. Gallagher, and S. Saunders (2004)
J. Biol. Chem. 279, 5604-5611
   Abstract »    Full Text »    PDF »
Immune Activation of NF-{kappa}B and JNK Requires Drosophila TAK1.
N. Silverman, R. Zhou, R. L. Erlich, M. Hunter, E. Bernstein, D. Schneider, and T. Maniatis (2003)
J. Biol. Chem. 278, 48928-48934
   Abstract »    Full Text »    PDF »
Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly.
B. L. Allen and A. C. Rapraeger (2003)
J. Cell Biol. 163, 637-648
   Abstract »    Full Text »    PDF »
Heparan Sulfate 6-O-Sulfotransferase Is Essential for Muscle Development in Zebrafish.
R. J. Bink, H. Habuchi, Z. Lele, E. Dolk, J. Joore, G.-J. Rauch, R. Geisler, S. W. Wilson, J. den Hertog, K. Kimata, et al. (2003)
J. Biol. Chem. 278, 31118-31127
   Abstract »    Full Text »    PDF »
QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling.
X. Ai, A.-T. Do, O. Lozynska, M. Kusche-Gullberg, U. Lindahl, and C. P. Emerson Jr. (2003)
J. Cell Biol. 162, 341-351
   Abstract »    Full Text »    PDF »
Molecular Cloning and Identification of 3'-Phosphoadenosine 5'-Phosphosulfate Transporter.
S. Kamiyama, T. Suda, R. Ueda, M. Suzuki, R. Okubo, N. Kikuchi, Y. Chiba, S. Goto, H. Toyoda, K. Saigo, et al. (2003)
J. Biol. Chem. 278, 25958-25963
   Abstract »    Full Text »    PDF »
Loss of HSulf-1 Up-regulates Heparin-binding Growth Factor Signaling in Cancer.
J. Lai, J. Chien, J. Staub, R. Avula, E. L. Greene, T. A. Matthews, D. I. Smith, S. H. Kaufmann, L. R. Roberts**, and V. Shridhar** (2003)
J. Biol. Chem. 278, 23107-23117
   Abstract »    Full Text »    PDF »
Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea.
A. Dabdoub, M. J. Donohue, A. Brennan, V. Wolf, M. Montcouquiol, D. A. Sassoon, J.-C. Hseih, J. S. Rubin, P. C. Salinas, and M. W. Kelley (2003)
Development 130, 2375-2384
   Abstract »    Full Text »    PDF »
Structural specificity of heparin binding in the fibroblast growth factor family of proteins.
R. Raman, G. Venkataraman, S. Ernst, V. Sasisekharan, and R. Sasisekharan (2003)
PNAS 100, 2357-2362
   Abstract »    Full Text »    PDF »
Cloning and Characterization of Two Extracellular Heparin-degrading Endosulfatases in Mice and Humans.
M. Morimoto-Tomita, K. Uchimura, Z. Werb, S. Hemmerich, and S. D. Rosen (2002)
J. Biol. Chem. 277, 49175-49185
   Abstract »    Full Text »    PDF »
Slug Is a Novel Downstream Target of MyoD. TEMPORAL PROFILING IN MUSCLE REGENERATION.
P. Zhao, S. Iezzi, E. Carver, D. Dressman, T. Gridley, V. Sartorelli, and E. P. Hoffman (2002)
J. Biol. Chem. 277, 30091-30101
   Abstract »    Full Text »    PDF »
Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification.
M. K. Gustafsson, H. Pan, D. F. Pinney, Y. Liu, A. Lewandowski, D. J. Epstein, and C. P. Emerson Jr. (2002)
Genes & Dev. 16, 114-126
   Abstract »    Full Text »    PDF »
Wnts, Signaling and Sulfates.
S. S. Blair (2001)
Sci. STKE 2001, pe32
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)