title: Sulf1 and Sulf2 expression in the nervous system and its role in limiting neurite outgrowth in vitro.
abstract: Sulf1 and Sulf2 are endosulfatases that cleave 6-O-sulphate groups from Heparan Sulphate Proteoglycans (HSPGs). Sulfation levels of HSPGs are critical for their role in modulating the activity of various growth factor receptors. Sulf1 and Sulf2 mRNAs were found to be widely expressed in the rodent nervous system and their full-length proteins were found in many types of neuronal perikarya and axons in the cerebral cortex, cerebellum, spinal cord and dorsal root ganglia (DRG) of adult rats. Sulf1/2 were also strongly expressed by cultured DRG neurons. To determine if blocking Sulf1 or Sulf2 activity affected neurite outgrowth in vitro, cultured DRG neurons were treated with neutralising antibodies to Sulf1 or Sulf2. Blocking Sulf1 and Sulf2 activity did not affect neurite outgrowth from cultured DRG neurons grown on a laminin/polylysine substrate but ameliorated the inhibitory effects of chondroitin sulphate proteoglycans (CSPGs) on neurite outgrowth. Blocking epidermal growth factor receptor (ErbB1) activity also improved neurite outgrowth in the presence of CSPGs, but the effects of ErbB1 antagonists and blocking SULFs were not additive. It is proposed that Sulf1, Sulf2 and ErbB1 are involved in the signalling pathway from CSPGs that leads to inhibition of neurite outgrowth and may regulate structural plasticity and regeneration in the nervous system.
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Mary T
authors.initials: MT
authors.lastname: Joy
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London NW1 OTU, UK.
authors.forename: Gerta
authors.initials: G
authors.lastname: Vrbova
authors.affiliation: Department of Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London NW1 OTU, UK. Electronic address: tdhoot@rvc.ac.uk.
authors.forename: Gurtej K
authors.initials: GK
authors.lastname: Dhoot
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Anderson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis; D005727:Ganglia, Spinal / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013429:Sulfatases / Q000096:biosynthesis*; D015238:Sulfotransferases / Q000096:biosynthesis*
chemical_list: C541485:EGFR protein, mouse; C483803:Egfr protein, rat; D066246:ErbB Receptors; C486773:Sulf1 protein, mouse; C507077:Sulf1 protein, rat; C547680:Sulf2 protein, rat; D015238:Sulfotransferases; C514911:Sulf2 protein, mouse; D013429:Sulfatases
keywords: CSPGs; Dorsal root ganglia; ErbB1; HSPGs; Neurite outgrowth; Sulf1; Sulf2