Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer’s-like axonal dystrophy. The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. Degeneration and Regeneration of the Nervous System. Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation. Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia. Synthesis of chondroitin sulfate E octasaccharide in a repeating region involving an acetamide auxiliary. Synthesis and interaction with midkine of biotinylated chondroitin sulfate tetrasaccharides. Synthetic approach towards sulfated chondroitin di-, tri- and tetrasaccharides corresponding to the repeating unit. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. A sulfated carbohydrate epitope inhibits axon regeneration after injury. Divergent synthesis of 48 heparan sulfate-based disaccharides and probing the specific sugar-fibroblast growth factor-1 interaction. α-Glycosylation by d-glucosamine-derived donors: synthesis of heparosan and heparin analogues that interact with mycobacterial heparin-binding hemagglutinin. Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction. Demystifying heparan sulfate-protein interactions. Protein tyrosine phosphatases: from genes, to function, to disease. Identification of novel binding sites for heparin in receptor protein-tyrosine phosphatase (RPTPσ): implications for proteoglycan signaling. Proteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension. The HSPGs syndecan and dallylike bind the receptor phosphatase LAR and exert distinct effects on synaptic development. Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. Heparan sulfate proteoglycans are ligands for receptor protein tyrosine phosphatase sigma. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. A role for proteoglycans in the guidance of a subset of pioneer axons in cultured embryos of the cockroach. Keratan sulfate restricts neural plasticity after spinal cord injury. Chondroitinase ABC promotes functional recovery after spinal cord injury. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Mammalian brain morphogenesis and midline axon guidance require heparan sulfate. Reactivation of ocular dominance plasticity in the adult visual cortex. Proteoglycan form and function: a comprehensive nomenclature of proteoglycans. Therefore, sulfation patterns determine the length of the glycosaminoglycan segment that bind to PTPRσ and define the fate of axonal regeneration through a mechanism involving PTPRσ, cortactin and autophagy. Such disruption is required and sufficient for dystrophic endball formation and inhibition of axonal regeneration. CS activates PTPRσ, which dephosphorylates cortactin-herein identified as a new PTPRσ substrate-and disrupts autophagy flux at the autophagosome–lysosome fusion step. Consequently, short and long stretches of natural CS and HS, respectively, bind to PTPRσ. Here, we have prepared a library of HS octasaccharides and, together with synthetic CS oligomers, we found that PTPRσ preferentially interacts with CS-E-a rare sulfation pattern in natural CS-and most HS oligomers bearing sulfate and sulfamate groups. CS inhibits axonal growth, while HS promotes it. Chondroitin sulfate (CS) and heparan sulfate (HS) are glycosaminoglycans that both bind the receptor-type protein tyrosine phosphatase PTPRσ, affecting axonal regeneration.
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