CSPG4
Description
The CSPG4 (chondroitin sulfate proteoglycan 4) is a protein-coding gene located on chromosome 15.
Chondroitin sulfate proteoglycan 4, also known as melanoma-associated chondroitin sulfate proteoglycan (MCSP) or neuron-glial antigen 2 (NG2), is a chondroitin sulfate proteoglycan that in humans is encoded by the CSPG4 gene. CSPG4 plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. It represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. CSPG4/NG2 is also a hallmark protein of oligodendrocyte progenitor cells (OPCs) and OPC dysfunction has been implicated as a candidate pathophysiological mechanism of familial schizophrenia. A research group investigating the role of genetics in schizophrenia, reported, two rare missense mutations in CSPG4 gene, segregating within families (CSPG4A131T and CSPG4V901G mutations). The researchers also demonstrate that the induced pluripotent stem cells (iPSCs)-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing, subcellular localization of the mutant NG2 protein, aberrant cellular morphology, and a decreased cell viability and myelination potential. In vivo diffusion tensor imaging of the brain of CSPG4A131T mutation carriers demonstrated a reduced white matter integrity compared to the unaffected sibling and matched general population controls.
CSPG4, also known as NG2, plays a vital role in cell proliferation and migration. It promotes endothelial cell motility during the development of blood vessels. CSPG4 can also inhibit the growth of nerve fibers and prevent the collapse of growth cones, which are important for nerve regeneration. This protein acts as a receptor for collagen alpha 2(VI) on the cell surface, enabling cells to move on this specific substrate. CSPG4 binds to growth factors and extracellular matrix proteases through its extracellular N-terminus, thereby modulating their activities. It may also regulate the breakdown and invasion of type I collagen through MPP16, contributing to the invasive properties of melanoma cells. Additionally, CSPG4 can modulate the plasminogen system by enhancing plasminogen activation and inhibiting angiostatin. CSPG4 functions as a signal transducing protein by binding to scaffolding and signaling proteins through its cytoplasmic C-terminus. This interaction can promote the formation of retraction fibers and cell polarization through the activation of Rho GTPases. Furthermore, CSPG4 can stimulate the adhesion and spreading of cells mediated by alpha-4, beta-1 integrins by recruiting and activating a signaling cascade involving CDC42, ACK1, and BCAR1. It can also activate the FAK and ERK1/ERK2 signaling cascades.
CSPG4 is also known as CSPG4A, HMW-MAA, MCSP, MCSPG, MEL-CSPG, MSK16, NG2.
