Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties.
Proteoglycans are expressed in various tissues on cell surfaces and in the extracellular matrix and display substantial heterogeneity of both protein and carbohydrate constituents. The functions of individual proteoglycans of the nervous system are not well characterized, partly because specific reagents which would permit their isolation are missing. We report here that the monoclonal antibody 473HD, which binds to the surface of early differentiation stages of murine astrocytes and oligodendrocytes, reacts with the chondroitin sulfate/dermatan sulfate hybrid epitope DSD-1 expressed on a central nervous system chondroitin sulfate proteoglycan designated DSD-1-PG. When purified from detergent-free postnatal days 7 to 14 mouse brain extracts, DSD-1-PG displays an apparent molecular mass between 800-1,000 kD with a prominent core glycoprotein of 350-400 kD. Polyclonal anti-DSD-1-PG antibodies and monoclonal antibody 473HD react with the same molecular species as shown by immunocytochemistry and sequential immunoprecipitation performed on postnatal mouse cerebellar cultures, suggesting that the DSD-1 epitope is restricted to one proteoglycan. DSD-1-PG promotes neurite outgrowth of embryonic day 14 mesencephalic and embryonic day 18 hippocampal neurons from rat, a process which can be blocked by monoclonal antibody 473HD and by enzymatic removal of the DSD-1-epitope. These results show that the hybrid glycosaminoglycan structure DSD-1 supports the morphological differentiation of central nervous system neurons.
Faissner
A
A
Department of Neurobiology, University of Heidelberg, Germany.
Clement
A
A
Lochter
A
A
Streit
A
A
Mandl
C
C
Schachner
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000276:immunology / Q000302:isolation & purification* / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D009414:Nerve Growth Factors / Q000276:immunology / Q000302:isolation & purification* / Q000494:pharmacology; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D011509:Proteoglycans / Q000276:immunology / Q000302:isolation & purification* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D000911:Antibodies, Monoclonal; D000939:Epitopes; D009414:Nerve Growth Factors; D011509:Proteoglycans; D002809:Chondroitin Sulfates