NG2 proteoglycan

NG2, or neural/glial antigen 2, is a rat integral membrane proteoglycan found in the plasma membrane of many diverse cell types.^[1] Homologous proteins in other species include human CSPG4, also known as melanoma-associated chondroitin sulfate proteoglycan (MCSP), Mouse AN2, and Sea urchin ECM3.^[2] This single-pass transmembrane molecule may be plasma membrane-bound or secreted and associated with the extracellular matrix.^[3] It is believed to play a role in functions such as cell adhesion, cell-cell and cell-ECM communication, migration and metastasis, proliferation, and axonal growth, guidance and regeneration. NG2-positive cells include oligodendrocyte progenitor cells (OPCs) and other progenitor cell populations, such as chondroblasts, myoblasts, and pericytes, as well as several different tumors including glioblastoma multiforme and melanoma.^{[4][5][6][7][8][9][10]}

Structure

NG2 cDNA contains 8,071 nucleotides corresponding to 2,325 amino acids. The entire protein is divided into three domains: a large extracellular domain (2,224 amino acids), a single transmembrane domain (25 amino acids), and a short cytoplasmic tail (76 amino acids). The extracellular domain is further subdivided into three subdomains: an N-terminal globular domain that contains several cysteines and is stabilized by intrachain disulfide bonds; a central domain to which the chondroitin sulfate moiety covalently binds; and a juxtamembrane domain also containing several cysteines. The core NG2 molecule is approximately 300 kDa and the addition of at least one chondroitin sulfate molecule results in a molecule that is 400 – 800 kDa.^[1]

Localization

NG2 is found both in the central nervous system (CNS) and peripherally in a variety of tissues. In the CNS, NG2 may be found on pericytes,^[4] various tumors including glioblastoma,^[5][6][7] and a population of progenitor cells known as polydendrocytes or oligodendrocyte precursor cells (OPCs).^[8] Peripherally, NG2 is found on chondroblasts, cardiomyocytes, aortic smooth muscle cells, myoblasts, and several different human tumors, including melanoma.^[9][10] Although NG2 is a single-pass transmembrane protein, it may also be released by proteolytic cleavage into the extracellular space where it associates with the extracellular matrix (ECM).^[3] The levels of NG2 have been shown to increase rapidly at areas of injury in the CNS, including in the area of the glial scar of spinal cord contusion injury.^{[2][11][12][13]}

Interacting molecules

NG2 interacts via its large extracellular domain with many factors in the extracellular space. Within its central extracellular domain, NG2 has a binding site for Type VI collagen as well as PDGF-AA. At its juxtamembrane domain, NG2 may interact with bFGF.^[14]

References