AN2, the mouse homologue of NG2, is a surface antigen on glial precursor cells implicated in control of cell migration

Abstract

Molecular studies have demonstrated that the murine AN2 antigen is the mouse homologue of the rat NG2 and human MCSP protein. The molecule is a single-pass transmembrane protein which carries a variable number of glyco- and glycosaminoglycan chains according to cell type and developmental stage. AN2/NG2 has two extracellular Laminin G-like domains which are classically involved in cell adhesion and recognition. It possesses a single PDZ binding motif in the short intracellular tail. The AN2/NG2 antigen is expressed by glial progenitor cells in developing and adult CNS and also by immature Schwann cells. Antibodies against AN2/NG2 inhibit the migration of antigen-positive cells in in vitro assays, suggesting that the molecule plays a role in migration. Many AN2/NG2-positive cells surround synapses in the developing and adult brain. A recently identified intracellular partner of AN2/NG2 is the glutamate receptor interacting protein GRIP, which binds to the GluRB subunit of the AMPA subclass of glutamate receptors. The AN2/NG2 protein may position AMPA receptors on perisynaptic glial cells towards active synapses by binding to a neuronal receptor. Many highly migratory neural tumors including melanomas express AN2/NG2. In the demyelinating disease Multiple Sclerosis, some patients synthesise antibodies against the protein. Such antibodies may play a pathological role by inhibiting the migration of oligodendrocyte progenitor cells to demyelinated axons thus blocking remyelination, as well as possibly interfering with glial neuronal signalling at synapses and nodes of Ranvier.