Proteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension.
AuthorsColes, Charlotte H
Tenney, Alan P
Sutton, Geoffrey C
Gallagher, John T
Jones, E Yvonne
Flanagan, John G
Aricescu, A Radu
AffiliationDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
MetadataShow full item record
AbstractHeparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) regulate numerous cell surface signaling events, with typically opposite effects on cell function. CSPGs inhibit nerve regeneration through receptor protein tyrosine phosphatase sigma (RPTPσ). Here we report that RPTPσ acts bimodally in sensory neuron extension, mediating CSPG inhibition and HSPG growth promotion. Crystallographic analyses of a shared HSPG-CSPG binding site reveal a conformational plasticity that can accommodate diverse glycosaminoglycans with comparable affinities. Heparan sulfate and analogs induced RPTPσ ectodomain oligomerization in solution, which was inhibited by chondroitin sulfate. RPTPσ and HSPGs colocalize in puncta on sensory neurons in culture, whereas CSPGs occupy the extracellular matrix. These results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.
CitationProteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension. 2011, 332 (6028):484-8 Science
- Modulation of Receptor Protein Tyrosine Phosphatase Sigma Increases Chondroitin Sulfate Proteoglycan Degradation through Cathepsin B Secretion to Enhance Axon Outgrowth.
- Authors: Tran AP, Sundar S, Yu M, Lang BT, Silver J
- Issue date: 2018 Jun 6
- PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration.
- Authors: Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG
- Issue date: 2009 Oct 23
- Heparan sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans (CSPGs) function as endocytic receptors for an internalizing anti-nucleic acid antibody.
- Authors: Park H, Kim M, Kim HJ, Lee Y, Seo Y, Pham CD, Lee J, Byun SJ, Kwon MH
- Issue date: 2017 Oct 30
- Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTPσ): Implications for proteoglycan signaling.
- Authors: Katagiri Y, Morgan AA, Yu P, Bangayan NJ, Junka R, Geller HM
- Issue date: 2018 Jul 20
- A new role for RPTPsigma in spinal cord injury: signaling chondroitin sulfate proteoglycan inhibition.
- Authors: Duan Y, Giger RJ
- Issue date: 2010 Feb 23