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 CSPG4gene.[1][2][3]
CSPG4 plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelialbasement membranes. It represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells.[3]
CSPG4/NG2 is also a hallmark protein of oligodendrocyte progenitor cells (OPCs)[4] and OPC dysfunction has been implicated as a candidate pathophysiological mechanism of familial schizophrenia.[5] 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 vivodiffusion 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.[6]
↑Luo W, Wang X, Kageshita T, Wakasugi S, Karpf AR, Ferrone S (May 2006). "Regulation of high molecular weight-melanoma associated antigen (HMW-MAA) gene expression by promoter DNA methylation in human melanoma cells". Oncogene. 25 (20): 2873–84. doi:10.1038/sj.onc.1209319. PMID16407841.
↑de Vrij FM, Bouwkamp CG, Gunhanlar N, Shpak G, Lendemeijer B, Baghdadi M, Gopalakrishna S, Ghazvini M, Li TM, Quadri M, Olgiati S, Breedveld GJ, Coesmans M, Mientjes E, de Wit T, Verheijen FW, Beverloo HB, Cohen D, Kok RM, Bakker PR, Nijburg A, Spijker AT, Haffmans PM, Hoencamp E, Bergink V, Vorstman JA, Wu T, Olde Loohuis LM, Amin N, Langen CD, Hofman A, Hoogendijk WJ, van Duijn CM, Ikram MA, Vernooij MW, Tiemeier H, Uitterlinden AG, Elgersma Y, Distel B, Gribnau J, White T, Bonifati V, Kushner SA (January 2018). "Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia". Molecular Psychiatry. doi:10.1038/s41380-017-0004-2. PMID29302076.
↑de Vrij FM, Bouwkamp CG, Gunhanlar N, Shpak G, Lendemeijer B, Baghdadi M, Gopalakrishna S, Ghazvini M, Li TM, Quadri M, Olgiati S, Breedveld GJ, Coesmans M, Mientjes E, de Wit T, Verheijen FW, Beverloo HB, Cohen D, Kok RM, Bakker PR, Nijburg A, Spijker AT, Haffmans PM, Hoencamp E, Bergink V, Vorstman JA, Wu T, Olde Loohuis LM, Amin N, Langen CD, Hofman A, Hoogendijk WJ, van Duijn CM, Ikram MA, Vernooij MW, Tiemeier H, Uitterlinden AG, Elgersma Y, Distel B, Gribnau J, White T, Bonifati V, Kushner SA (January 2018). "Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia". Molecular Psychiatry. doi:10.1038/s41380-017-0004-2. PMID29302076.
Further reading
Kirschfink M, Blase L, Engelmann S, Schwartz-Albiez R (February 1997). "Secreted chondroitin sulfate proteoglycan of human B cell lines binds to the complement protein C1q and inhibits complex formation of C1". Journal of Immunology. 158 (3): 1324–31. PMID9013976.
Iida J, Meijne AM, Oegema TR, Yednock TA, Kovach NL, Furcht LT, McCarthy JB (March 1998). "A role of chondroitin sulfate glycosaminoglycan binding site in alpha4beta1 integrin-mediated melanoma cell adhesion". The Journal of Biological Chemistry. 273 (10): 5955–62. doi:10.1074/jbc.273.10.5955. PMID9488735.
Iida J, Pei D, Kang T, Simpson MA, Herlyn M, Furcht LT, McCarthy JB (June 2001). "Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen". The Journal of Biological Chemistry. 276 (22): 18786–94. doi:10.1074/jbc.M010053200. PMID11278606.
Staub E, Hinzmann B, Rosenthal A (September 2002). "A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan defines a new protein family". FEBS Letters. 527 (1–3): 114–8. doi:10.1016/S0014-5793(02)03195-2. PMID12220645.
Stegmüller J, Werner H, Nave KA, Trotter J (February 2003). "The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. Implications for glial-neuronal signaling". The Journal of Biological Chemistry. 278 (6): 3590–8. doi:10.1074/jbc.M210010200. PMID12458226.
Legg J, Jensen UB, Broad S, Leigh I, Watt FM (December 2003). "Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in human interfollicular epidermis". Development. 130 (24): 6049–63. doi:10.1242/dev.00837. PMID14573520.
Ghali L, Wong ST, Tidman N, Quinn A, Philpott MP, Leigh IM (February 2004). "Epidermal and hair follicle progenitor cells express melanoma-associated chondroitin sulfate proteoglycan core protein". The Journal of Investigative Dermatology. 122 (2): 433–42. doi:10.1046/j.0022-202X.2004.22207.x. PMID15009727.
Makagiansar IT, Williams S, Dahlin-Huppe K, Fukushi J, Mustelin T, Stallcup WB (December 2004). "Phosphorylation of NG2 proteoglycan by protein kinase C-alpha regulates polarized membrane distribution and cell motility". The Journal of Biological Chemistry. 279 (53): 55262–70. doi:10.1074/jbc.M411045200. PMID15504744.
Petrini S, Tessa A, Stallcup WB, Sabatelli P, Pescatori M, Giusti B, Carrozzo R, Verardo M, Bergamin N, Columbaro M, Bernardini C, Merlini L, Pepe G, Bonaldo P, Bertini E (November 2005). "Altered expression of the MCSP/NG2 chondroitin sulfate proteoglycan in collagen VI deficiency". Molecular and Cellular Neurosciences. 30 (3): 408–17. doi:10.1016/j.mcn.2005.08.005. PMID16169245.
Brekke C, Lundervold A, Enger PØ, Brekken C, Stålsett E, Pedersen TB, Haraldseth O, Krüger PG, Bjerkvig R, Chekenya M (February 2006). "NG2 expression regulates vascular morphology and function in human brain tumours". NeuroImage. 29 (3): 965–76. doi:10.1016/j.neuroimage.2005.08.026. PMID16253523.
