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.

Subscribe

Logo for

Science 326 (5952): 592-596

Copyright © 2009 by the American Association for the Advancement of Science

PTP{sigma} Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration

Yingjie Shen,1,* Alan P. Tenney,1,*,{dagger} Sarah A. Busch,2 Kevin P. Horn,2 Fernando X. Cuascut,2 Kai Liu,3 Zhigang He,3 Jerry Silver,2 John G. Flanagan1,{ddagger}

Abstract: Chondroitin sulfate proteoglycans (CSPGs) present a barrier to axon regeneration. However, no specific receptor for the inhibitory effect of CSPGs has been identified. We showed that a transmembrane protein tyrosine phosphatase, PTP{sigma}, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTP{sigma}. In culture, PTP{sigma}–/– neurons show reduced inhibition by CSPG. A PTP{sigma} fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTP{sigma} gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTP{sigma} can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.

1 Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA.
3 Division of Neuroscience, Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger}Present address: Motor Neuron Center, Columbia University, New York, NY 10032, USA.

{ddagger} To whom correspondence should be addressed. E-mail: flanagan{at}hms.harvard.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Nogo Receptor Homolog NgR2 Expressed in Sensory DRG Neurons Controls Epidermal Innervation by Interaction with Versican.
B. E. Baumer, A. Kurz, S. C. Borrie, S. Sickinger, M. T. Dours-Zimmermann, D. R. Zimmermann, and C. E. Bandtlow (2014)
J. Neurosci. 34, 1633-1646
   Abstract »    Full Text »    PDF »
Combination of Engineered Schwann Cell Grafts to Secrete Neurotrophin and Chondroitinase Promotes Axonal Regeneration and Locomotion after Spinal Cord Injury.
H. Kanno, Y. Pressman, A. Moody, R. Berg, E. M. Muir, J. H. Rogers, H. Ozawa, E. Itoi, D. D. Pearse, and M. B. Bunge (2014)
J. Neurosci. 34, 1838-1855
   Abstract »    Full Text »    PDF »
CLAC-P/Collagen Type XXV Is Required for the Intramuscular Innervation of Motoneurons during Neuromuscular Development.
T. Tanaka, T. Wakabayashi, H. Oizumi, S. Nishio, T. Sato, A. Harada, D. Fujii, Y. Matsuo, T. Hashimoto, and T. Iwatsubo (2014)
J. Neurosci. 34, 1370-1379
   Abstract »    Full Text »    PDF »
Protein tyrosine phosphatase {sigma} targets apical junction complex proteins in the intestine and regulates epithelial permeability.
R. Murchie, C.-H. Guo, A. Persaud, A. Muise, and D. Rotin (2014)
PNAS 111, 693-698
   Abstract »    Full Text »    PDF »
Chondroitin Sulfate Proteoglycans Potently Inhibit Invasion and Serve as a Central Organizer of the Brain Tumor Microenvironment.
D. J. Silver, F. A. Siebzehnrubl, M. J. Schildts, A. T. Yachnis, G. M. Smith, A. A. Smith, B. Scheffler, B. A. Reynolds, J. Silver, and D. A. Steindler (2013)
J. Neurosci. 33, 15603-15617
   Abstract »    Full Text »    PDF »
Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains.
G. Dick, C. L. Tan, J. N. Alves, E. M. E. Ehlert, G. M. Miller, L. C. Hsieh-Wilson, K. Sugahara, A. Oosterhof, T. H. van Kuppevelt, J. Verhaagen, et al. (2013)
J. Biol. Chem. 288, 27384-27395
   Abstract »    Full Text »    PDF »
Perilesional Treatment with Chondroitinase ABC and Motor Training Promote Functional Recovery After Stroke in Rats.
L. Gherardini, M. Gennaro, and T. Pizzorusso (2013)
Cereb Cortex
   Abstract »    Full Text »    PDF »
Nerve Regeneration Restores Supraspinal Control of Bladder Function after Complete Spinal Cord Injury.
Y.-S. Lee, C.-Y. Lin, H.-H. Jiang, M. DePaul, V. W. Lin, and J. Silver (2013)
J. Neurosci. 33, 10591-10606
   Abstract »    Full Text »    PDF »
Infarct-Derived Chondroitin Sulfate Proteoglycans Prevent Sympathetic Reinnervation after Cardiac Ischemia-Reperfusion Injury.
R. T. Gardner and B. A. Habecker (2013)
J. Neurosci. 33, 7175-7183
   Abstract »    Full Text »    PDF »
Atypical Protein Kinase C and Par3 Are Required for Proteoglycan-Induced Axon Growth Inhibition.
S.-i. Lee, W. Zhang, M. Ravi, M. Weschenfelder, M. Bastmeyer, and J. M. Levine (2013)
J. Neurosci. 33, 2541-2554
   Abstract »    Full Text »    PDF »
Cell intrinsic and extrinsic factors contribute to enhance neural circuit reconstruction following transplantation in Parkinsonian mice.
J. Kauhausen, L. H. Thompson, and C. L. Parish (2013)
J. Physiol. 591, 77-91
   Abstract »    Full Text »    PDF »
Chondroitin Sulfate Is a Crucial Determinant for Skeletal Muscle Development/Regeneration and Improvement of Muscular Dystrophies.
T. Mikami, S. Koyama, Y. Yabuta, and H. Kitagawa (2012)
J. Biol. Chem. 287, 38531-38542
   Abstract »    Full Text »    PDF »
Intra-Axonal Translation of RhoA Promotes Axon Growth Inhibition by CSPG.
B. A. Walker, S.-J. Ji, and S. R. Jaffrey (2012)
J. Neurosci. 32, 14442-14447a
   Abstract »    Full Text »    PDF »
p53 Regulates the Neuronal Intrinsic and Extrinsic Responses Affecting the Recovery of Motor Function following Spinal Cord Injury.
E. M. Floriddia, K. I. Rathore, A. Tedeschi, G. Quadrato, A. Wuttke, J.-M. Lueckmann, K. A. Kigerl, P. G. Popovich, and S. Di Giovanni (2012)
J. Neurosci. 32, 13956-13970
   Abstract »    Full Text »    PDF »
Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats.
J. J. Hill, K. Jin, X. O. Mao, L. Xie, and D. A. Greenberg (2012)
PNAS 109, 9155-9160
   Abstract »    Full Text »    PDF »
Chondroitin Sulfate Proteoglycans Down-regulate Spine Formation in Cortical Neurons by Targeting Tropomyosin-related Kinase B (TrkB) Protein.
D. Kurihara and T. Yamashita (2012)
J. Biol. Chem. 287, 13822-13828
   Abstract »    Full Text »    PDF »
A sulfated carbohydrate epitope inhibits axon regeneration after injury.
J. M. Brown, J. Xia, B. Zhuang, K.-S. Cho, C. J. Rogers, C. I. Gama, M. Rawat, S. E. Tully, N. Uetani, D. E. Mason, et al. (2012)
PNAS 109, 4768-4773
   Abstract »    Full Text »    PDF »
Thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase.
K. Takahashi, R. L. Mernaugh, D. B. Friedman, R. Weller, N. Tsuboi, H. Yamashita, V. Quaranta, and T. Takahashi (2012)
PNAS 109, 1985-1990
   Abstract »    Full Text »    PDF »
Chondroitinase ABC reduces time to muscle reinnervation and improves functional recovery after sciatic nerve transection in rats.
M. J. Sabatier, B. N. To, S. Rose, J. Nicolini, and A. W. English (2012)
J Neurophysiol 107, 747-757
   Abstract »    Full Text »    PDF »
Structural insights into the homology and differences between mouse protein tyrosine phosphatase-sigma and human protein tyrosine phosphatase-sigma.
L. Hou, J. Wang, Y. Zhou, J. Li, Y. Zang, and J. Li (2011)
Acta Biochim Biophys Sin 43, 977-988
   Abstract »    Full Text »    PDF »
Extrinsic and intrinsic determinants of nerve regeneration.
T. A. Ferguson and Y.-J. Son (2011)
Journal of Tissue Engineering 2, 2041731411418392
   Abstract »    Full Text »    PDF »
Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury.
S. Imagama, K. Sakamoto, R. Tauchi, R. Shinjo, T. Ohgomori, Z. Ito, H. Zhang, Y. Nishida, N. Asami, S. Takeshita, et al. (2011)
J. Neurosci. 31, 17091-17102
   Abstract »    Full Text »    PDF »
Leukocyte Common Antigen-Related Phosphatase Is a Functional Receptor for Chondroitin Sulfate Proteoglycan Axon Growth Inhibitors.
D. Fisher, B. Xing, J. Dill, H. Li, H. H. Hoang, Z. Zhao, X.-L. Yang, R. Bachoo, S. Cannon, F. M. Longo, et al. (2011)
J. Neurosci. 31, 14051-14066
   Abstract »    Full Text »    PDF »
Regulation of protein tyrosine phosphatases by reversible oxidation.
A. Ostman, J. Frijhoff, A. Sandin, and F.-D. Bohmer (2011)
J. Biochem. 150, 345-356
   Abstract »    Full Text »    PDF »
Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons.
P. Parikh, Y. Hao, M. Hosseinkhani, S. B. Patil, G. W. Huntley, M. Tessier-Lavigne, and H. Zou (2011)
PNAS 108, E99-E107
   Abstract »    Full Text »    PDF »
Integrin Activation Promotes Axon Growth on Inhibitory Chondroitin Sulfate Proteoglycans by Enhancing Integrin Signaling.
C. L. Tan, J. C. F. Kwok, R. Patani, C. ffrench-Constant, S. Chandran, and J. W. Fawcett (2011)
J. Neurosci. 31, 6289-6295
   Abstract »    Full Text »    PDF »
Proteoglycan-Specific Molecular Switch for RPTP{sigma} Clustering and Neuronal Extension.
C. H. Coles, Y. Shen, A. P. Tenney, C. Siebold, G. C. Sutton, W. Lu, J. T. Gallagher, E. Y. Jones, J. G. Flanagan, and A. R. Aricescu (2011)
Science 332, 484-488
   Abstract »    Full Text »    PDF »
The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar.
A. L. Hawthorne, H. Hu, B. Kundu, M. P. Steinmetz, C. J. Wylie, E. S. Deneris, and J. Silver (2011)
J. Neurosci. 31, 5605-5616
   Abstract »    Full Text »    PDF »
The Cytoplasmic Adaptor Protein Caskin Mediates Lar Signal Transduction during Drosophila Motor Axon Guidance.
Y.-L. Weng, N. Liu, A. DiAntonio, and H. T. Broihier (2011)
J. Neurosci. 31, 4421-4433
   Abstract »    Full Text »    PDF »
Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules.
E.-M. Hur, I. H. Yang, D.-H. Kim, J. Byun, Saijilafu, W.-L. Xu, P. R. Nicovich, R. Cheong, A. Levchenko, N. Thakor, et al. (2011)
PNAS 108, 5057-5062
   Abstract »    Full Text »    PDF »
Taxol Facilitates Axon Regeneration in the Mature CNS.
V. Sengottuvel, M. Leibinger, M. Pfreimer, A. Andreadaki, and D. Fischer (2011)
J. Neurosci. 31, 2688-2699
   Abstract »    Full Text »    PDF »
Targets for Neural Repair Therapies After Stroke.
S. T. Carmichael (2010)
Stroke 41, S124-S126
   Abstract »    Full Text »    PDF »
Mammalian Target of Rapamycin (mTOR) Activation Increases Axonal Growth Capacity of Injured Peripheral Nerves.
N. Abe, S. H. Borson, M. J. Gambello, F. Wang, and V. Cavalli (2010)
J. Biol. Chem. 285, 28034-28043
   Abstract »    Full Text »    PDF »
Guidance Molecules in Axon Regeneration.
R. J. Giger, E. R. Hollis II, and M. H. Tuszynski (2010)
Cold Spring Harb Perspect Biol 2, a001867
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus K3 and K5 Proteins Block Distinct Steps in Transendothelial Migration of Effector Memory CD4+ T Cells by Targeting Different Endothelial Proteins.
T. D. Manes, S. Hoer, W. A. Muller, P. J. Lehner, and J. S. Pober (2010)
J. Immunol. 184, 5186-5192
   Abstract »    Full Text »    PDF »
Trans-synaptic Adhesions between Netrin-G Ligand-3 (NGL-3) and Receptor Tyrosine Phosphatases LAR, Protein-tyrosine Phosphatase {delta} (PTP{delta}), and PTP{sigma} via Specific Domains Regulate Excitatory Synapse Formation.
S. K. Kwon, J. Woo, S. Y. Kim, H. Kim, and E. Kim (2010)
J. Biol. Chem. 285, 13966-13978
   Abstract »    Full Text »    PDF »
A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition of Neuronal Regeneration.
L. C. Usher, A. Johnstone, A. Erturk, Y. Hu, D. Strikis, I. B. Wanner, S. Moorman, J. W. Lee, J. Min, H. H. Ha, et al. (2010)
J. Neurosci. 30, 4693-4706
   Abstract »    Full Text »    PDF »
A New Role for RPTP{sigma} in Spinal Cord Injury: Signaling Chondroitin Sulfate Proteoglycan Inhibition.
Y. Duan and R. J. Giger (2010)
Science Signaling 3, pe6
   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