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J Biol Chem, Vol. 273, Issue 43, 28444-28453, October 23, 1998
From the The neural chondroitin sulfate (CS) proteoglycan
(PG) DSD-1-PG was originally identified with the monoclonal antibody
(mAb) 473HD. It promotes neurite outgrowth of hippocampal neurons when coated as a substrate in the presence of polycations. This effect is
inhibited by mAb 473HD that specifically recognizes the DSD-1 epitope.
The DSD-1 epitope is also detectable in CS-C and CS-D preparations from
shark cartilage but not in other chondroitin sulfates that are
structurally related and differ in their sulfation patterns.
Non-sulfated DSD-1-PG and chemically desulfated CS-D were not
recognized by mAb 473HD, suggesting that the DSD-1 epitope depends on
sulfation. It was possible to enrich DSD-1 epitope-bearing carbohydrates and D disaccharide units from CS-C and CS-D preparations on a mAb 473HD affinity matrix. This indicates that the DSD-1 epitope
represents a distinct glycosaminoglycan structure containing D units.
The analysis of glycosaminoglycan digestion products by high pressure
liquid chromatography revealed that DSD-1-PG preparations contain a
unique D disaccharide unit as well as an A, a C, and a non-sulfated
disaccharide unit. In neurite outgrowth assays with hippocampal
neurons, substrate-bound CS-D promoted neurite outgrowth, whereas CS-A,
CS-B, or CS-C did not. This effect of CS-D was inhibited by mAb 473HD.
DSD-1 epitope-enriched fractions obtained from CS-D and CS-C promoted
neurite outgrowth, whereas CS-C had no such effect prior to enrichment
on the mAb 473HD matrix. Based on these findings we conclude that the
DSD-1 epitope by itself is sufficient to promote neurite outgrowth and
that this activity is possibly associated with D motifs.
The DSD-1 Carbohydrate Epitope Depends on Sulfation, Correlates
with Chondroitin Sulfate D Motifs, and Is Sufficient to Promote
Neurite Outgrowth
,,¶
Department of Neurobiology, University of
Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany, the
§ Department of Biochemistry, Kobe Pharmaceutical
University, Higashinada-ku 20, Kobe 658-8558, Japan, and
¶ Laboratoire de Neurobiologie du Développment et
de la Régéneration, UPR 1352, Centre de Neurochimie du CNRS
et Université Louis Pasteur, F-67084 Strasbourg, France
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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