Contactin-1 is a functional receptor for neuroregulatory chondroitin sulfate-E.
Chondroitin sulfate (CS) plays critical roles in central nervous system development and regeneration, and individual modifications of CS form a "sulfation code" that regulates growth factor signaling or neuronal growth. Although we have shown that CS-E polysaccharide, but not CS-A or -C polysaccharide, has an inherent ability to promote neurite outgrowth toward primary neurons, its molecular mechanism remains elusive. Here, we show the involvement of a plasma membrane-tethered cell adhesion molecule, contactin-1 (CNTN-1), in CS-E-mediated neurite extension in a mouse neuroblastoma cell line and primary hippocampal neurons. CS-E, but not CS-A, -C, or heparan sulfate, engaged CNTN-1 with significant affinity and induced intracellular signaling downstream of CNTN-1, indicating that CS-E is a selective ligand for a potential CS receptor, CNTN-1, leading to neurite outgrowth. Our data provide the first evidence that biological functions of CS are exerted through the CS receptor-mediated signaling pathway(s).
Mikami
Tadahisa
T
Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558 and CREST, the Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
Yasunaga
Daiki
D
Kitagawa
Hiroshi
H
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000819:agonists / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism* / Q000494:pharmacology; D058967:Contactin 1; D058966:Contactins; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; C548670:Cntn1 protein, mouse; D058967:Contactin 1; D058966:Contactins; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D002809:Chondroitin Sulfates