NG2, A Large Membrane-Spanning Proteoglycan

Abstract

NG2 is a large chondroitin sulfate proteoglycan which was originally identified on rat neural cell lines that could not be classified as being strictly neuronal or glial based on their electrophysiological properties. Immunocytochemical studies of tissue sections and cells in primary cultures revealed the expression of NG2 on dividing progenitor cells of the 02A glial lineage and on immature cells of mesenchymal origin. From biochemical analysis, NG2 was shown to be initially synthesized as a 260kDa core protein which was glycosylated to yield a mature core glycoprotein of 300kDa. It is estimated that each core contains 3-4 chondroitin sulfate chains. The primary structure of the NG2 core protein was determined from cDNA clones. The open reading frame codes for a protein of 2325 amino acids which can be divided into a large extracellular domain, a transmembrane domain, and a short cytoplasmic domain. The ectodomain can be further divided into three subdomains: two cysteine-rich regions separated by a region rich in serine-glycine pairs. One particular motif of 200 amino acids is repeated four times in the ectodomain. A portion of the sequence resembles the putative calcium-binding region of the cadherins. The overall sequence of NG2 has little homology with other known sequences, suggesting that NG2 is a novel integral membrane proteoglycan.