title: Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation.
abstract: Perineuronal nets (PNs) are lattice-like condensations of the extracellular matrix (ECM) that envelop synapses and decorate the surface of subsets of neurons in the CNS. Previous work has suggested that, despite the fact that PNs themselves are not visualized until later in development, some PN component molecules are expressed in the rodent CNS even before synaptogenesis. In the adult mammalian brain, monoclonal antibody Cat-315 recognizes a glycoform of aggrecan, a major component of PNs. In primary cortical cultures, a Cat-315-reactive chondroitin sulfate proteoglycan (CSPG) is also expressed on neuronal surfaces and is secreted into culture media as early as 24 h after plating. In this study, we show that in primary cortical cultures, the Cat-315 CSPG detected in early neural development is expressed in extrasynaptic sites prior to synapse formation. This suggests that ECM components in the CNS, as in the neuromuscular junction (NMJ), may prepattern neuronal surfaces prior to innervation. We further show that while the Cat-315-reactive carbohydrate decorates aggrecan in the adult, it decorates a different CSPG in the developing CNS. Using receptor protein tyrosine phosphatase beta (RPTPbeta/protein tyrosine phosphatase zeta) knock-out mice and immunoprecipitation techniques, we demonstrate here that in the developing rodent brain Cat-315 recognizes RPTPbeta isoforms. Our further examination of the Cat-315 epitope suggests that it is an O-mannose linked epitope in the HNK-1 family. The presence of the Cat-315 reactive carbohydrate on different PN components--RPTPbeta and aggrecan--at different stages of synapse development suggests a potential role for this neuron-specific carbohydrate motif in synaptogenesis.
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Dino
authors.forename: S
authors.initials: S
authors.lastname: Harroch
authors.forename: S
authors.initials: S
authors.lastname: Hockfield
authors.forename: R T
authors.initials: RT
authors.lastname: Matthews
mesh_terms: D053674:Aggrecans / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D018959:CD57 Antigens / Q000737:chemistry / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology* / Q000254:growth & development* / Q000648:ultrastructure; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005109:Extracellular Matrix / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D053674:Aggrecans; D000911:Antibodies, Monoclonal; D018959:CD57 Antigens; D011508:Chondroitin Sulfate Proteoglycans; D000939:Epitopes; D017027:Protein Tyrosine Phosphatases; C516896:Ptprz1 protein, mouse; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5