Semaphorin 5A Is a Bifunctional Axon Guidance Cue Regulated by Heparan and Chondroitin Sulfate Proteoglycans
| Autor: | Katherine L. Peer, Alex L. Kolodkin, Yu Yamaguchi, David W. Sretavan, Michael J. Hansen, Onanong Chivatakarn, David B. Kantor, Stephen F. Oster, Roman J. Giger, John G. Flanagan, Masaru Inatani |
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| Rok vydání: | 2004 |
| Předmět: |
animal structures
Neuroscience(all) Nerve Tissue Proteins Context (language use) Semaphorins Inhibitory postsynaptic potential Cell Line Rats Sprague-Dawley Glycosaminoglycan Mice Organ Culture Techniques Semaphorin Mesencephalon Pregnancy Animals Humans Thrombospondin Dose-Response Relationship Drug biology Chemistry General Neuroscience Membrane Proteins Axons Transmembrane protein Rats Cell biology carbohydrates (lipids) Chondroitin Sulfate Proteoglycans nervous system Proteoglycan Biochemistry biology.protein Female Axon guidance Heparan Sulfate Proteoglycans |
| Zdroj: | Neuron. 44:961-975 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2004.12.002 |
| Popis: | The response of neuronal growth cones to axon guidance cues depends on the developmental context in which these cues are encountered. We show here that the transmembrane protein semaphorin 5A (Sema5A) is a bifunctional guidance cue exerting both attractive and inhibitory effects on developing axons of the fasciculus retroflexus, a diencephalon fiber tract associated with limbic function. The thrombospondin repeats of Sema5A physically interact with the glycosaminoglycan portion of both chondroitin sulfate proteoglycans (CSPGs) and heparan sulfate proteoglycans (HSPGs). CSPGs function as precisely localized extrinsic cues that convert Sema5A from an attractive to an inhibitory guidance cue. Therefore, glycosaminoglycan bound guidance cues provide a molecular mechanism for CSPG-mediated inhibition of axonal extension. Further, axonal HSPGs are required for Sema5A-mediated attraction, suggesting that HSPGs are components of functional Sema5A receptors. Thus, neuronal responses to Sema5A are proteoglycan dependent and interpreted according to the biological context in which this membrane bound guidance cue is presented. |
| Databáze: | OpenAIRE |
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