title: Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain.
abstract: The role of type IIA receptor protein tyrosine phosphatases (RPTPs), which includes LAR, RPTPσ and RPTPδ, in the nervous system is becoming increasingly recognized. Evidence supports a significant role for these RPTPs during the development of the nervous system as well as after injury, and mutations in RPTPs are associated with human disease. However, a major open question is the nature of the ligands that interact with type IIA RPTPs in the adult brain. Candidates include several different proteins as well as the glycosaminoglycan chains of proteoglycans. In order to investigate this problem, we used a receptor affinity probe assay with RPTPσ-AP fusion proteins on sections of adult mouse brain and to cultured neurons. Our results demonstrate that the major binding sites for RPTPσ in adult mouse brain are on neurons and are not proteoglycan GAG chains, as RPTPσ binding overlaps with the neuronal marker NeuN and was not significantly altered by treatments which eliminate chondroitin sulfate, heparan sulfate, or both. We also demonstrate no overlap of binding of RPTPσ with perineuronal nets, and a unique modulation of RPTPσ binding to brain by divalent cations. Our data therefore point to neuronal proteins, rather than CSPGs, as being the ligands for RPTPσ in the adult, uninjured brain.
authors: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Jae-Hyuk
authors: JH
authors: Yi
authors: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Yasuhiro
authors: Y
authors: Katagiri
authors: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Panpan
authors: P
authors: Yu
authors: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Jacob
authors: J
authors: Lourie
authors: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Nathanael J
authors: NJ
authors: Bangayan
authors: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Aviva J
authors: AJ
authors: Symes
authors: Developmental Neurobiology Section, Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: geller@helix.nih.gov.
authors: Herbert M
authors: HM
authors: Geller
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*
chemical_list: D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Chondroitin sulfate; Heparan sulfate; Protein tyrosine phosphatase; Proteoglycan; Receptor affinity probe assay