Carbohydrate-protein interactions between HNK-1-reactive sulfoglucuronyl glycolipids and the proteoglycan lectin domain mediate neuronal cell adhesion and neurite outgrowth.
Lecticans, a family of chondroitin sulfate proteoglycans, represent the largest group of proteoglycans expressed in the nervous system. We previously showed that the C-type lectin domains of lecticans bind two classes of sulfated cell surface glycolipids, sulfatides and HNK-1-reactive sulfoglucuronylglycolipids (SGGLs). In this paper, we demonstrate that the interaction between the lectin domain of brevican, a nervous system-specific lectican, and cell surface SGGLs acts as a novel cell recognition system that promotes neuronal adhesion and neurite outgrowth. The Ig chimera of the brevican lectin domain bind to the surface of SGGL-expressing rat hippocampal neurons. The substrate of the brevican chimera promotes adhesion and neurite outgrowth of hippocampal neurons. The authentic, full-length brevican also promotes neuronal cell adhesion and neurite outgrowth. These activities of brevican substrates are neutralized by preincubation of cells with HNK-1 monoclonal antibodies and by pretreatment of the brevican substrates with purified SGGLs. Brevican and HNK-1 carbohydrates are coexpressed in specific layers of the developing hippocampus where axons from entorhinal neurons elongate. Our observations suggest that cell surface SGGLs and extracellular lecticans comprise a novel cell-substrate recognition system operating in the developing nervous system.
Miura
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The Burnham Institute, La Jolla, California 92037, USA.
Ethell
I M
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Yamaguchi
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Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D058581:Brevican; D018959:CD57 Antigens / Q000276:immunology / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006017:Glycolipids / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C546939:Bcan protein, rat; D058581:Brevican; D018959:CD57 Antigens; D011508:Chondroitin Sulfate Proteoglycans; D006017:Glycolipids; D007136:Immunoglobulins; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins