The role of the NG2 proteoglycan in OPC and CNS network function

Abstract

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).

Adult oligodendrocyte progenitor cells – Multifaceted regulators of the CNS in health and disease

“…The lack of an OPC-specific NG2 knockout model questions whether these findings are mediated exclusively by OPCs. A follow up study found that OPCs express neuromodulatory factor neuronal Pentraxin 2 (Nptx2), which affects AMPAR stability and trafficking at the cell surface (Sakry and Trotter, 2015). Taken together, the data suggests that OPC-derived factors can affect neuronal network activity, but the importance of this bidirectional OPC-neuron communication requires further investigation.…”

The regulatory mechanisms of NG2/CSPG4 expression

“…In particular, high levels are detected in NG2-glia of the central nervous system (CNS) [18, 19]. NG2-glia are non-neuronal, non-vascular cells that underlie a complex interplay of epigenetic mechanisms and transcription factors in distinct developmental stages [20, 21].…”

Increased NG2 and SOX2 expression is associated with high-grade choroid plexus tumors

“…NG2 has been postulated to function as a cell adhesion molecule, which was supported by the observation that the extracellular region between the transmembrane domain and the laminin G/neurexin/sex-hormone-binding globulin domains binds to integrins and collagen V and VI (26). Previous studies have revealed a more defined role for NG2 in brain homeostasis including intracellular functions in oligodendrocyte progenitor cells, which modulate migration, gene expression and α-amino-3-hydroxy-5-methyl-4-isoxazol epropionic acid receptor clustering (15,24,27).…”

“…NG2 has been identified to be expressed during development in extraneural progenitor cell types, including mesenchymal stem cells, chondroblasts, osteoblasts, immature keratinocytes, muscle progenitors and melanocytes (23). Additionally, NG2 serves a role in cell viability and angiogenesis (24). NG2 deficiency during early development results in the loss of pericyte-endothelium association and defective formation of basement membranes in blood vessels (25).…”