Roles of CSGalNAcT1, a key enzyme in regulation of CS synthesis, in neuronal regeneration and plasticity
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AbstractChondroitin sulfate (CS) is a sulfated glycosaminoglycan composed of a long chain of repeating disaccharide units that are attached to core proteins, resulting in CS proteoglycans (CSPGs). In the mature brain, CS is concentrated in perineuronal nets (PNNs), which are extracellular structures that surround synapses and regulate synaptic plasticity. In addition, CS is rapidly synthesized after CNS injury to create a physical and chemical barrier that inhibits axon growth. Most previous studies used a bacterial CS-degrading enzyme to investigate the physiological roles of CS. Recent studies have shown that CS is synthesized by more than 15 enzymes, all of which have been characterized in vitro. Here we focus on one of those enzymes, CSGalNAcT1 (T1). We produced T1 knockout mice (KO), which show extensive axon regeneration following spinal cord injury, as well as the loss of onset of ocular dominance plasticity. These results from T1KO mice suggest important roles for extracellular CS in the brain regarding neuronal plasticity and axon regeneration.
CitationIgarashi, M., Takeuchi, K., & Sugiyama, S. (2018). Roles of CSGalNAcT1, a key enzyme in regulation of CS synthesis, in neuronal regeneration and plasticity. Neurochemistry International, 119, 77–83. doi:10.1016/j.neuint.2017.10.001
SponsorsWe thank K. Mineta, PhD (King Abdullah University of Science and Technology, Saudi Arabia) for support in Fig. 1B. This work was supported in part by grants TOGONO (Comprehensive Brain Science Network) on Innovative Areas from MEXT of Japan (M.I.), Uehara Memorial Foundation (to M.I.), and KAKENHI from MEXT of Japan and from JSPS (#17023019, #22240040, and #24111515 to M.I., #24110503 and #26110703 to K.T., #22700330 and #26430010 to S.S.).