CSPG4 explained

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.^{[1] [2] [3]}

Function

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.

Implications in disease

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 (CSPG4^A131T and CSPG4^V901G mutations). The researchers also demonstrate that the induced pluripotent stem cells (iPSCs)-derived OPCs from CSPG4^A131T 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 CSPG4^A131T mutation carriers demonstrated a reduced white matter integrity compared to the unaffected sibling and matched general population controls.^[6]

See also

• NG2-glia

Further reading

• Kirschfink M, Blase L, Engelmann S, Schwartz-Albiez R . 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 . February 1997 . 10.4049/jimmunol.158.3.1324 . 9013976 . free .
• Iida J, Meijne AM, Oegema TR, Yednock TA, Kovach NL, Furcht LT, McCarthy JB . A role of chondroitin sulfate glycosaminoglycan binding site in alpha4beta1 integrin-mediated melanoma cell adhesion . The Journal of Biological Chemistry . 273 . 10 . 5955–62 . March 1998 . 9488735 . 10.1074/jbc.273.10.5955 . free .
• Eisenmann KM, McCarthy JB, Simpson MA, Keely PJ, Guan JL, Tachibana K, Lim L, Manser E, Furcht LT, Iida J . Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas . Nature Cell Biology . 1 . 8 . 507–13 . December 1999 . 10587647 . 10.1038/70302 . 16876663 .
• Barritt DS, Pearn MT, Zisch AH, Lee SS, Javier RT, Pasquale EB, Stallcup WB . The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane-spanning proteoglycan NG2 . Journal of Cellular Biochemistry . 79 . 2 . 213–24 . August 2000 . 10967549 . 3501957 . 10.1002/1097-4644(20001101)79:2<213::AID-JCB50>3.0.CO;2-G .
• Iida J, Pei D, Kang T, Simpson MA, Herlyn M, Furcht LT, McCarthy JB . Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen . The Journal of Biological Chemistry . 276 . 22 . 18786–94 . June 2001 . 11278606 . 10.1074/jbc.M010053200 . free .
• Staub E, Hinzmann B, Rosenthal A . A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan defines a new protein family . FEBS Letters . 527 . 1–3 . 114–8 . September 2002 . 12220645 . 10.1016/S0014-5793(02)03195-2 . 43541248 .
• Stegmüller J, Werner H, Nave KA, Trotter J . 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 . February 2003 . 12458226 . 10.1074/jbc.M210010200 . free .
• Legg J, Jensen UB, Broad S, Leigh I, Watt FM . Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in human interfollicular epidermis . Development . 130 . 24 . 6049–63 . December 2003 . 14573520 . 10.1242/dev.00837 . 10336770 .
• Ghali L, Wong ST, Tidman N, Quinn A, Philpott MP, Leigh IM . Epidermal and hair follicle progenitor cells express melanoma-associated chondroitin sulfate proteoglycan core protein . The Journal of Investigative Dermatology . 122 . 2 . 433–42 . February 2004 . 15009727 . 10.1046/j.0022-202X.2004.22207.x . free .
• Fukushi J, Makagiansar IT, Stallcup WB . NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin . Molecular Biology of the Cell . 15 . 8 . 3580–90 . August 2004 . 15181153 . 491820 . 10.1091/mbc.E04-03-0236 .
• Yang J, Price MA, Neudauer CL, Wilson C, Ferrone S, Xia H, Iida J, Simpson MA, McCarthy JB . Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms . The Journal of Cell Biology . 165 . 6 . 881–91 . June 2004 . 15210734 . 2172406 . 10.1083/jcb.200403174 .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–32 . July 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . September 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Makagiansar IT, Williams S, Dahlin-Huppe K, Fukushi J, Mustelin T, Stallcup WB . 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 . December 2004 . 15504744 . 10.1074/jbc.M411045200 . free .
• 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 . Altered expression of the MCSP/NG2 chondroitin sulfate proteoglycan in collagen VI deficiency . Molecular and Cellular Neurosciences . 30 . 3 . 408–17 . November 2005 . 16169245 . 10.1016/j.mcn.2005.08.005 . 36610297 .
• Brekke C, Lundervold A, Enger PØ, Brekken C, Stålsett E, Pedersen TB, Haraldseth O, Krüger PG, Bjerkvig R, Chekenya M . NG2 expression regulates vascular morphology and function in human brain tumours . NeuroImage . 29 . 3 . 965–76 . February 2006 . 16253523 . 10.1016/j.neuroimage.2005.08.026 . 42026544 . 1956/2370 . free .
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD . Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry . Journal of Proteome Research . 4 . 6 . 2070–80 . 2006 . 16335952 . 1850943 . 10.1021/pr0502065 .

Notes and References

1. Pluschke G, Vanek M, Evans A, Dittmar T, Schmid P, Itin P, Filardo EJ, Reisfeld RA . Molecular cloning of a human melanoma-associated chondroitin sulfate proteoglycan . Proceedings of the National Academy of Sciences of the United States of America . 93 . 18 . 9710–5 . September 1996 . 8790396 . 38494 . 10.1073/pnas.93.18.9710 . 1996PNAS...93.9710P . free .
2. Luo W, Wang X, Kageshita T, Wakasugi S, Karpf AR, Ferrone S . 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 . May 2006 . 16407841 . 10.1038/sj.onc.1209319 . 39073910 .
3. Web site: Entrez Gene: CSPG4 chondroitin sulfate proteoglycan 4.
4. Nishiyama A, Dahlin KJ, Prince JT, Johnstone SR, Stallcup WB . The primary structure of NG2, a novel membrane-spanning proteoglycan . The Journal of Cell Biology . 114 . 2 . 359–71 . July 1991 . 1906475 . 2289079 . 10.1083/jcb.114.2.359.
5. 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 . Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia . Molecular Psychiatry . 24 . 5 . 757–771 . January 2018 . 29302076 . 6755981 . 10.1038/s41380-017-0004-2 .
6. 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 . Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia . Molecular Psychiatry . 24 . 5 . 757–771 . January 2018 . 29302076 . 6755981 . 10.1038/s41380-017-0004-2 .