In the normal mammalian CNS, the NG2 proteoglycan is expressed by oligodendrocyte precursor cells (OPC) but not by any other neural cell-type. NG2 is a type-1 membrane protein, exerting multiple roles in the CNS including intracellular signaling within the OPC, with effects on migration, cytoskeleton interaction and target gene regulation. It has been recently shown that the extracellular region of NG2, in addition to an adhesive function, acts as a soluble ECM component with the capacity to alter defined neuronal network properties. This region of NG2 is thus endowed with neuromodulatory properties. In order to generate biologically active fragments yielding these properties, the sequential cleavage of the NG2 protein by α- and γ-secretases occurs. The basal level of constitutive cleavage is stimulated by neuronal network activity. This processing leads to 4 major NG2 fragments which all have been associated with distinct biological functions. Here we summarize these functions, focusing on recent discoveries and their implications for the CNS. This article is part of a Special Issue entitled SI:NG2-glia(Invited only).
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http://dx.doi.org/10.1016/j.brainres.2015.06.003 | DOI Listing |
Adv Sci (Weinh)
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Department of Neonatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
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Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria.
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Pathology Unit, Department of Mental Health and Physic and Preventive Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.
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Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80445, USA. Electronic address:
The extracellular matrix (ECM) provides critical biochemical and structural cues that regulate neural development. Chondroitin sulfate proteoglycans (CSPGs), a major ECM component, have been implicated in modulating oligodendrocyte precursor cell (OPC) proliferation, migration, and maturation, but their specific roles in oligodendrocyte lineage cell (OLC) development and myelination in vivo remain poorly understood. Here, we use zebrafish as a model system to investigate the spatiotemporal dynamics of ECM deposition and CSPG localization during central nervous system (CNS) development, with a focus on their relationship to OLCs.
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Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200135, China.
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