NG2-positive cells in CNS function and the pathological role of antibodies against NG2 in demyelinating diseases

Abstract

NG2 is expressed by a variety of immature glia in the CNS including oligodendrocyte progenitor cells, paranodal astrocytes and perisynaptic glia. The protein has a large extracellular domain with two LNS/Lam G domains at the N-terminus and a short intracellular tail with a PDZ-recognition domain at the C-terminus. Experiments suggest that the protein plays a role in migration. The PDZ protein GRIP was identified as an intracellular binding partner of NG2 in immature glial cells. A complex is formed between GRIP, NG2 and the AMPA class of glutamate receptors: this may position these glial receptors towards sites of neuronal glutamate release at synapses and during myelination. Identification of neuronal receptors and links to the cytoskeleton of NG2 is of critical importance. Some Mutiple Sclerosis patients have autoantibodies to NG2 in the cerebral spinal fluid: such antibodies could interfere with remyelination by lysing oligodendrocyte progenitor cells or blocking their migration but may also cause pathology by disrupting glial–neuronal signalling at synapses and paranodes.