 |
Previous Article | Next Article 
Journal of Neuroscience, Vol 14, 7616-7628, Copyright © 1994 by Society for Neuroscience
Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan
CL Dou and JM Levine
Department of Neurobiology and Behavior, State University of New York at Stony Brook 11794.
The chondroitin sulfate proteoglycans (CSPGs) have been implicated as both
positive and negative modulators of axonal growth; however, the functional
properties of only a few specific CSPGs have been investigated. Here we
demonstrate that NG2, an integral membrane CSPG expressed on the surfaces
of glial progenitor cells, inhibits neurite growth from neonatal rat
cerebellar granule neurons when presented to the cells as a component of
the substrate. Growth inhibition occurred when NG2 was mixed with either
laminin or L1, two potent promoters of axonal extension. Moreover, when
given a choice between surfaces coated with NG2 and laminin or L1, the
axons of the cerebellar neurons extended preferentially on laminin or L1
and avoided areas of the substrate containing NG2. The NG2 proteoglycan
inhibited neurite growth after digestion with chondroitinase ABC,
demonstrating that the inhibitory activity is a property of the core
protein and not the covalently attached chondroitin sulfate
glycosaminoglycan chains. NG2 also inhibited neurite growth from embryonic
rat dorsal root ganglia neurons on substrates containing laminin. However,
when the sensory neurons were plated onto surfaces containing the L1
glycoprotein and NG2, neurite growth was not inhibited. These results
demonstrate that the NG2 proteoglycan provides an unfavorable substrate for
axonal growth. Cells that express this proteoglycan in vivo may participate
in axonal guidance by defining areas of the developing CNS that are
nonpermissive for axonal extension from specific classes of developing
neurons.
This article has been cited by other articles:

|
 |

|
 |
 
L. M. Carter, M. L. Starkey, S. F. Akrimi, M. Davies, S. B. McMahon, and E. J. Bradbury
The Yellow Fluorescent Protein (YFP-H) Mouse Reveals Neuroprotection as a Novel Mechanism Underlying Chondroitinase ABC-Mediated Repair after Spinal Cord Injury
J. Neurosci.,
December 24, 2008;
28(52):
14107 - 14120.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. W. Barritt, M. Davies, F. Marchand, R. Hartley, J. Grist, P. Yip, S. B. McMahon, and E. J. Bradbury
Chondroitinase ABC Promotes Sprouting of Intact and Injured Spinal Systems after Spinal Cord Injury.
J. Neurosci.,
October 18, 2006;
26(42):
10856 - 10867.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. T Filbin
Recapitulate development to promote axonal regeneration: good or bad approach?
Phil Trans R Soc B,
September 29, 2006;
361(1473):
1565 - 1574.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. P Liu, W. B.J Cafferty, S. O Budel, and S. M Strittmatter
Extracellular regulators of axonal growth in the adult central nervous system
Phil Trans R Soc B,
September 29, 2006;
361(1473):
1593 - 1610.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Nakanishi, S. Aono, K. Hirano, Y. Kuroda, M. Ida, Y. Tokita, F. Matsui, and A. Oohira
Identification of Neurite Outgrowth-promoting Domains of Neuroglycan C, a Brain-specific Chondroitin Sulfate Proteoglycan, and Involvement of Phosphatidylinositol 3-Kinase and Protein Kinase C Signaling Pathways in Neuritogenesis
J. Biol. Chem.,
August 25, 2006;
281(34):
24970 - 24978.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Yang, R. Suzuki, S. B. Daniels, C. B. Brunquell, C. J. Sala, and A. Nishiyama
NG2 glial cells provide a favorable substrate for growing axons.
J. Neurosci.,
April 5, 2006;
26(14):
3829 - 3839.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. K. Huang, G. R. Phillips, A. D. Roth, L. Pedraza, W. Shan, W. Belkaid, S. Mi, A. Fex-Svenningsen, L. Florens, J. R. Yates III, et al.
Glial Membranes at the Node of Ranvier Prevent Neurite Outgrowth
Science,
December 16, 2005;
310(5755):
1813 - 1817.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Schwab, P. P. Monnier, H. J. Schluesener, S. Conrad, R. Beschorner, L. Chen, R. Meyermann, and B. K. Mueller
Central Nervous System Injury-Induced Repulsive Guidance Molecule Expression in the Adult Human Brain
Arch Neurol,
October 1, 2005;
62(10):
1561 - 1568.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Bao, T. Mikami, S. Yamada, A. Faissner, T. Muramatsu, and K. Sugahara
Heparin-binding Growth Factor, Pleiotrophin, Mediates Neuritogenic Activity of Embryonic Pig Brain-derived Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains
J. Biol. Chem.,
March 11, 2005;
280(10):
9180 - 9191.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. H. Larsen, J. E. Wells, W. B. Stallcup, G. Opdenakker, and V. W. Yong
Matrix Metalloproteinase-9 Facilitates Remyelination in Part by Processing the Inhibitory NG2 Proteoglycan
J. Neurosci.,
December 3, 2003;
23(35):
11127 - 11135.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. L. Jones, D. Sajed, and M. H. Tuszynski
Axonal Regeneration through Regions of Chondroitin Sulfate Proteoglycan Deposition after Spinal Cord Injury: A Balance of Permissiveness and Inhibition
J. Neurosci.,
October 15, 2003;
23(28):
9276 - 9288.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Li and S. M. Strittmatter
Delayed Systemic Nogo-66 Receptor Antagonist Promotes Recovery from Spinal Cord Injury
J. Neurosci.,
May 15, 2003;
23(10):
4219 - 4227.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. N. G. Anderson, K. Ohta, M. M. Quick, A. Fleming, R. Keynes, and D. Tannahill
Molecular analysis of axon repulsion by the notochord
Development,
March 15, 2003;
130(6):
1123 - 1133.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. M. Ughrin, Z. J. Chen, and J. M. Levine
Multiple Regions of the NG2 Proteoglycan Inhibit Neurite Growth and Induce Growth Cone Collapse
J. Neurosci.,
January 1, 2003;
23(1):
175 - 186.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. K. Kwon, J. F. Borisoff, and W. Tetzlaff
Molecular Targets for Therapeutic Intervention after Spinal Cord Injury
Mol. Interv.,
July 1, 2002;
2(4):
244 - 258.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. L. Jones, Y. Yamaguchi, W. B. Stallcup, and M. H. Tuszynski
NG2 Is a Major Chondroitin Sulfate Proteoglycan Produced after Spinal Cord Injury and Is Expressed by Macrophages and Oligodendrocyte Progenitors
J. Neurosci.,
April 1, 2002;
22(7):
2792 - 2803.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. A. Asher, D. A. Morgenstern, M. C. Shearer, K. H. Adcock, P. Pesheva, and J. W. Fawcett
Versican Is Upregulated in CNS Injury and Is a Product of Oligodendrocyte Lineage Cells
J. Neurosci.,
March 15, 2002;
22(6):
2225 - 2236.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. G. Becker and T. Becker
Repellent Guidance of Regenerating Optic Axons by Chondroitin Sulfate Glycosaminoglycans in Zebrafish
J. Neurosci.,
February 1, 2002;
22(3):
842 - 853.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Ichijo and I. Kawabata
Roles of the Telencephalic Cells and their Chondroitin Sulfate Proteoglycans in Delimiting an Anterior Border of the Retinal Pathway
J. Neurosci.,
December 1, 2001;
21(23):
9304 - 9314.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Martin, A. K. Levine, Z. J. Chen, Y. Ughrin, and J. M. Levine
Deposition of the NG2 Proteoglycan at Nodes of Ranvier in the Peripheral Nervous System
J. Neurosci.,
October 15, 2001;
21(20):
8119 - 8128.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Chernousov, R. C. Stahl, and D. J. Carey
Schwann Cell Type V Collagen Inhibits Axonal Outgrowth and Promotes Schwann Cell Migration via Distinct Adhesive Activities of the Collagen and Noncollagen Domains
J. Neurosci.,
August 15, 2001;
21(16):
6125 - 6135.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Lemons, J. D. Sandy, D. K. Anderson, and D. R. Howland
Intact Aggrecan and Fragments Generated by Both Aggrecanse and Metalloproteinase-Like Activities Are Present in the Developing and Adult Rat Spinal Cord and Their Relative Abundance Is Altered by Injury
J. Neurosci.,
July 1, 2001;
21(13):
4772 - 4781.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. S. Ramer, I. Duraisingam, J. V. Priestley, and S. B. McMahon
Two-Tiered Inhibition of Axon Regeneration at the Dorsal Root Entry Zone
J. Neurosci.,
April 15, 2001;
21(8):
2651 - 2660.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Schneider, F. Bosse, D. D'Urso, H.-W. Muller, M. W. Sereda, K.-A. Nave, A. Niehaus, T. Kempf, M. Schnolzer, and J. Trotter
The AN2 Protein Is a Novel Marker for the Schwann Cell Lineage Expressed by Immature and Nonmyelinating Schwann Cells
J. Neurosci.,
February 1, 2001;
21(3):
920 - 933.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Inatani, H. Tanihara, A. Oohira, Y. Otori, A. Nishida, M. Honjo, N. Kido, and Y. Honda
Neuroglycan C, a Neural Tissue-Specific Transmembrane Chondroitin Sulfate Proteoglycan, in Retinal Neural Network Formation
Invest. Ophthalmol. Vis. Sci.,
December 1, 2000;
41(13):
4338 - 4346.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
C. E. Bandtlow and D. R. Zimmermann
Proteoglycans in the Developing Brain: New Conceptual Insights for Old Proteins
Physiol Rev,
October 1, 2000;
80(4):
1267 - 1290.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. A. Asher, D. A. Morgenstern, P. S. Fidler, K. H. Adcock, A. Oohira, J. E. Braistead, J. M. Levine, R. U. Margolis, J. H. Rogers, and J. W. Fawcett
Neurocan Is Upregulated in Injured Brain and in Cytokine-Treated Astrocytes
J. Neurosci.,
April 1, 2000;
20(7):
2427 - 2438.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. P. Wu, C.-J. Siao, W. Lu, T.-C. Sung, M. A. Frohman, P. Milev, T. H. Bugge, J. L. Degen, J. M. Levine, R. U. Margolis, et al.
The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate
J. Cell Biol.,
March 20, 2000;
148(6):
1295 - 1304.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Chung, J. Taylor, D. Shum, and S. Chan
Axon routing at the optic chiasm after enzymatic removal of chondroitin sulfate in mouse embryos
Development,
January 6, 2000;
127(12):
2673 - 2683.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M Schmalfeldt, C. Bandtlow, M. Dours-Zimmermann, K. Winterhalter, and D. Zimmermann
Brain derived versican V2 is a potent inhibitor of axonal growth
J. Cell Sci.,
January 3, 2000;
113(5):
807 - 816.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
R. J. McKeon, M. J. Jurynec, and C. R. Buck
The Chondroitin Sulfate Proteoglycans Neurocan and Phosphacan Are Expressed by Reactive Astrocytes in the Chronic CNS Glial Scar
J. Neurosci.,
December 15, 1999;
19(24):
10778 - 10788.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Condic, D. M. Snow, and P. C. Letourneau
Embryonic Neurons Adapt to the Inhibitory Proteoglycan Aggrecan by Increasing Integrin Expression
J. Neurosci.,
November 15, 1999;
19(22):
10036 - 10043.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. S. Fidler, K. Schuette, R. A. Asher, A. Dobbertin, S. R. Thornton, Y. Calle-Patino, E. Muir, J. M. Levine, H. M. Geller, J. H. Rogers, et al.
Comparing Astrocytic Cell Lines that Are Inhibitory or Permissive for Axon Growth: the Major Axon-Inhibitory Proteoglycan Is NG2
J. Neurosci.,
October 15, 1999;
19(20):
8778 - 8788.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. P. Niederost, D. R. Zimmermann, M. E. Schwab, and C. E. Bandtlow
Bovine CNS Myelin Contains Neurite Growth-Inhibitory Activity Associated with Chondroitin Sulfate Proteoglycans
J. Neurosci.,
October 15, 1999;
19(20):
8979 - 8989.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. T. Fitch, C. Doller, C. K. Combs, G. E. Landreth, and J. Silver
Cellular and Molecular Mechanisms of Glial Scarring and Progressive Cavitation: In Vivo and In Vitro Analysis of Inflammation-Induced Secondary Injury after CNS Trauma
J. Neurosci.,
October 1, 1999;
19(19):
8182 - 8198.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Niehaus, J. Stegmuller, M. Diers-Fenger, and J. Trotter
Cell-Surface Glycoprotein of Oligodendrocyte Progenitors Involved in Migration
J. Neurosci.,
June 15, 1999;
19(12):
4948 - 4961.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Garwood, O. Schnadelbach, A. Clement, K. Schutte, A. Bach, and A. Faissner
DSD-1-Proteoglycan Is the Mouse Homolog of Phosphacan and Displays Opposing Effects on Neurite Outgrowth Dependent on Neuronal Lineage
J. Neurosci.,
May 15, 1999;
19(10):
3888 - 3899.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Hoffman-Kim, A. D. Lander, and S. Jhaveri
Patterns of Chondroitin Sulfate Immunoreactivity in the Developing Tectum Reflect Regional Differences in Glycosaminoglycan Biosynthesis
J. Neurosci.,
August 1, 1998;
18(15):
5881 - 5890.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. A. Spillmann, C. E. Bandtlow, F. Lottspeich, F. Keller, and M. E. Schwab
Identification and Characterization of a Bovine Neurite Growth Inhibitor (bNI-220)
J. Biol. Chem.,
July 24, 1998;
273(30):
19283 - 19293.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z.-C. Xiao, U. Bartsch, R. K. Margolis, G. Rougon, D. Montag, and M. Schachner
Isolation of a Tenascin-R Binding Protein from Mouse Brain Membranes. A PHOSPHACAN-RELATED CHONDROITIN SULFATE PROTEOGLYCAN
J. Biol. Chem.,
December 19, 1997;
272(51):
32092 - 32101.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Faissner
REVIEW {blacksquare} : Glial Derived Extracellular Matrix Components: Important Roles in Axon Growth and Guidance
Neuroscientist,
November 1, 1997;
3(6):
371 - 380.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
L Erskine and C. McCaig
Integrated interactions between chondroitin sulphate proteoglycans and weak dc electric fields regulate nerve growth cone guidance in vitro
J. Cell Sci.,
January 8, 1997;
110(16):
1957 - 1965.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
N Maeda and M Noda
6B4 proteoglycan/phosphacan is a repulsive substratum but promotes morphological differentiation of cortical neurons
Development,
January 2, 1996;
122(2):
647 - 658.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Watanabe, N. Maeda, F. Matsui, Y. Kushima, M. Noda, and A. Oohira
Neuroglycan C, a Novel Membrane-spanning Chondroitin Sulfate Proteoglycan That Is Restricted to the Brain
J. Biol. Chem.,
November 10, 1995;
270(45):
26876 - 26882.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Shioi, M. N. Pangalos, J. A. Ripellino, D. Vassilacopoulou, C. Mytilineou, R. U. Margolis, and N. K. Robakis
The Alzheimer Amyloid Precursor Proteoglycan (Appican) Is Present in Brain and Is Produced by Astrocytes but Not by Neurons in Primary Neural Cultures
J. Biol. Chem.,
May 19, 1995;
270(20):
11839 - 11844.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|

|