NG2-expressing cells in the nervous system: role of the proteoglycan in migration and glial-neuron interaction

The NG2 glycoprotein is a type I membrane protein expressed in the developing and adult central nervous system (CNS) by subpopulations of glia including oligodendroglial precursor cells (OPCs), and in the developing CNS additionally by pericytes. In the mouse CNS, expression of NG2 protein is already observed at embryonic day 13 and peaks between postnatal days 8 and 12. NG2+ cells persist in grey and white matter in adult mouse brain: cells in the developing and adult brain show clear differences in migration, cell-cycle length and lineage restriction. Several groups have provided evidence that subpopulations of NG2+ cells can generate neurons in vivo. Neuronal stimulation in the developing and adult hippocampus leads to Ca 2+ signals in apposing NG2+ glia, suggesting that these cells may modulate synaptic activity, and NG2+ cells often ensheath synapses. The structure of the protein with two N-terminal LamininG/Neurexin/Sex-hormone-binding globulin domains suggests a role in adhesion. The C-terminal PSD-95/DiscsLarge/Zona Occludens-1 (PDZ)-binding motif has been found to associate with several PDZ proteins including the Glutamate Receptor Interacting Protein GRIP: NG2 may thus act to position AMPA receptors on glia towards sites of neuronal glutamate release. Furthermore, the NG2 proteoglycan plays a role in cell migration and spreading and associates with actin-containing cytoskeletal structures.