S100B
S100 calcium binding protein B or S100B is a protein of the S-100 protein family.
S100 proteins are localized in the cytoplasm and nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 21q22.3.
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[edit] Function
S100B is glial-specific and is expressed primarily by astrocytes, but not all astrocytes express S100B. It has been shown [1] that S100B is only expressed by a subtype of mature astrocytes that ensheath blood vessels and by NG2-expressing cells.
This protein may function in neurite extension, proliferation of melanoma cells, stimulation of Ca2+ fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. In the developing CNS it acts as a neurotrophic factor and neuronal survival protein. In the adult organism it is usually elevated due to nervous system damage, which makes it a potential clinical marker. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer's disease, Down's syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes.[2]
[edit] Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Normal[3] |
| Citrobacter infection | Normal[4] |
| All tests and analysis from[5][6] |
Model organisms have been used in the study of S100B function. A conditional knockout mouse line, called S100btm1a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty three tests were carried out on mutant mice, but no significant abnormalities were observed.[5]
[edit] Interactions
S100B has been shown to interact with S100A11,[13] IQGAP1,[14] S100 calcium binding protein A1,[13][15][16] Tau protein,[17][18] S100A6,[13][16] PGM1,[19] VAV1,[20] AHNAK[21] and P53.[22]
[edit] Diagnostic use
S100B is secreted by astrocytes or can spill from injured cells and enter the extracellular space or bloodstream. Serum levels of S100B increase in patients during the acute phase of brain damage. Over the last decade, S100B has emerged as a candidate peripheral biomarker of blood-brain barrier (BBB) permeability and CNS injury. Elevated S100B levels accurately reflect the presence of neuropathological conditions including traumatic head injury or neurodegenerative diseases. Normal S100B levels reliably exclude major CNS pathology. Its potential clinical use in the therapeutic decision making process is substantiated by a vast body of literature validating variations in serum 100B levels with standard modalities for prognosticating the extent of CNS damage: alterations in neuroimaging, cerebrospinal pressure, and other brain molecular markers (neuron specific enolase, glial fibrillary acidic protein. However, more importantly, S100B levels have been reported to rise prior to any detectable changes in intracerebral pressure, neuroimaging, and neurological examination findings. Thus, the major advantage of using S100B is that elevations in serum or CSF levels provide a sensitive measure for determining CNS injury at the molecular level before gross changes develop, enabling timely delivery of crucial medical intervention before irreversible damage occurs. S100B serum levels are elevated before seizures suggesting that BBB leakage may be an early event in seizure development. [23] An extremely important application of serum S100B testing is in the selection of patients with minor head injury who do not need further neuroradiological evaluation, as studies comparing CT scans and S100B levels have demonstrated S100B values below 0.12 ng/mL are associated with low risk of obvious neuroradiological changes (such as intracranial hemorrhage or brain swelling) or significant clinical sequelae. The excellent negative predictive value of S100B in several neurological conditions is due to the fact that serum S100B levels reflect blood-brain barrier permeability changes even in absence of neuronal injury[24] [25].
[edit] References
- ^ Lin, Doris D. Wang; Angélique Bordey (December 2008). "The astrocyte odyssey". Prog. Neurobiol. 86 (11): 342–67.
- ^ "Entrez Gene: S100B S100 calcium binding protein B". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6285.
- ^ "Salmonella infection data for S100b". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MCFR/salmonella-challenge/.
- ^ "Citrobacter infection data for S100b". Wellcome Trust Sanger Institute. http://www.sanger.ac.uk/mouseportal/phenotyping/MCFR/citrobacter-challenge/.
- ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
- ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ "International Knockout Mouse Consortium". http://www.knockoutmouse.org/martsearch/search?query=S100b.
- ^ "Mouse Genome Informatics". http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4432844.
- ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M. et al. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMID 21677750.
- ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21722353.
- ^ a b c Deloulme, J C; Assard N, Mbele G O, Mangin C, Kuwano R, Baudier J (November 2000). "S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo". J. Biol. Chem. (UNITED STATES) 275 (45): 35302–10. doi:10.1074/jbc.M003943200. ISSN 0021-9258. PMID 10913138.
- ^ Mbele, Gaelh Ouengue; Deloulme Jean Christophe, Gentil Benoît Jean, Delphin Christian, Ferro Myriam, Garin Jérôme, Takahashi Miyoko, Baudier Jacques (December 2002). "The zinc- and calcium-binding S100B interacts and co-localizes with IQGAP1 during dynamic rearrangement of cell membranes". J. Biol. Chem. (United States) 277 (51): 49998–50007. doi:10.1074/jbc.M205363200. ISSN 0021-9258. PMID 12377780.
- ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- ^ a b Yang, Q; O'Hanlon D, Heizmann C W, Marks A (February 1999). "Demonstration of heterodimer formation between S100B and S100A6 in the yeast two-hybrid system and human melanoma". Exp. Cell Res. (UNITED STATES) 246 (2): 501–9. doi:10.1006/excr.1998.4314. ISSN 0014-4827. PMID 9925766.
- ^ Yu, W H; Fraser P E (April 2001). "S100beta interaction with tau is promoted by zinc and inhibited by hyperphosphorylation in Alzheimer's disease". J. Neurosci. (United States) 21 (7): 2240–6. PMID 11264299.
- ^ Baudier, J; Cole R D (April 1988). "Interactions between the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase II". J. Biol. Chem. (UNITED STATES) 263 (12): 5876–83. ISSN 0021-9258. PMID 2833519.
- ^ Landar, A; Caddell G, Chessher J, Zimmer D B (September 1996). "Identification of an S100A1/S100B target protein: phosphoglucomutase". Cell Calcium (SCOTLAND) 20 (3): 279–85. doi:10.1016/S0143-4160(96)90033-0. ISSN 0143-4160. PMID 8894274.
- ^ Fackler, O T; Luo W, Geyer M, Alberts A S, Peterlin B M (June 1999). "Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions". Mol. Cell (UNITED STATES) 3 (6): 729–39. doi:10.1016/S1097-2765(01)80005-8. ISSN 1097-2765. PMID 10394361.
- ^ Gentil, B J; Delphin C, Mbele G O, Deloulme J C, Ferro M, Garin J, Baudier J (June 2001). "The giant protein AHNAK is a specific target for the calcium- and zinc-binding S100B protein: potential implications for Ca2+ homeostasis regulation by S100B". J. Biol. Chem. (United States) 276 (26): 23253–61. doi:10.1074/jbc.M010655200. ISSN 0021-9258. PMID 11312263.
- ^ Lin, Jing; Yang Qingyuan, Yan Zhe, Markowitz Joseph, Wilder Paul T, Carrier France, Weber David J (August 2004). "Inhibiting S100B restores p53 levels in primary malignant melanoma cancer cells". J. Biol. Chem. (United States) 279 (32): 34071–7. doi:10.1074/jbc.M405419200. ISSN 0021-9258. PMID 15178678.
- ^ Marchi N, Angelov L, Masaryk T, et al. (April 2007). "Seizure-promoting effect of blood-brain barrier disruption". Epilepsia 48 (4): 732–42. doi:10.1111/j.1528-1167.2007.00988.x. PMID 17319915.
- ^ Czeisler BM, Janigro D (June 2006). "Reading and writing the blood-brain barrier: relevance to therapeutics". Recent patents on CNS drug discovery 1 (2): 157–73. PMID 18221201.
- ^ Marchi N, Cavaglia M, Fazio V, Bhudia S, Hallene K, Janigro D (April 2004). "Peripheral markers of blood-brain barrier damage". Clinica Chimica Acta 342 (1–2): 1–12. doi:10.1016/j.cccn.2003.12.008. PMID 15026262.
[edit] Further reading
- Schäfer BW, Heizmann CW (1996). "The S100 family of EF-hand calcium-binding proteins: functions and pathology". Trends Biochem. Sci. 21 (4): 134–40. PMID 8701470.
- Garbuglia M, Verzini M, Sorci G, et al. (2000). "The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments". Braz. J. Med. Biol. Res. 32 (10): 1177–85. PMID 10510252.
- Rothermundt M, Peters M, Prehn JH, Arolt V (2003). "S100B in brain damage and neurodegeneration". Microsc. Res. Tech. 60 (6): 614–32. doi:10.1002/jemt.10303. PMID 12645009.
- Michetti F, Gazzolo D (2004). "S100B testing in pregnancy". Clin. Chim. Acta 335 (1–2): 1–7. doi:10.1016/S0009-8981(03)00243-2. PMID 12927678.
- Raabe A, Kopetsch O, Woszczyk A, et al. (2004). "Serum S-100B protein as a molecular marker in severe traumatic brain injury". Restor. Neurol. Neurosci. 21 (3–4): 159–69. PMID 14530578.
- Sen J, Belli A (2007). "S100B in neuropathologic states: the CRP of the brain?". J. Neurosci. Res. 85 (7): 1373–80. doi:10.1002/jnr.21211. PMID 17348038.
- Morii K, Tanaka R, Takahashi Y, et al. (1991). "Structure and chromosome assignment of human S100 alpha and beta subunit genes". Biochem. Biophys. Res. Commun. 175 (1): 185–91. doi:10.1016/S0006-291X(05)81218-5. PMID 1998503.
- Allore RJ, Friend WC, O'Hanlon D, et al. (1990). "Cloning and expression of the human S100 beta gene". J. Biol. Chem. 265 (26): 15537–43. PMID 2394738.
- Duncan AM, Higgins J, Dunn RJ, et al. (1989). "Refined sublocalization of the human gene encoding the beta subunit of the S100 protein (S100B) and confirmation of a subtle t(9;21) translocation using in situ hybridization". Cytogenet. Cell Genet. 50 (4): 234–5. doi:10.1159/000132767. PMID 2530061.
- Baudier J, Cole RD (1988). "Interactions between the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase II". J. Biol. Chem. 263 (12): 5876–83. PMID 2833519.
- Allore R, O'Hanlon D, Price R, et al. (1988). "Gene encoding the beta subunit of S100 protein is on chromosome 21: implications for Down syndrome". Science 239 (4845): 1311–3. doi:10.1126/science.2964086. PMID 2964086.
- Jensen R, Marshak DR, Anderson C, et al. (1985). "Characterization of human brain S100 protein fraction: amino acid sequence of S100 beta". J. Neurochem. 45 (3): 700–5. doi:10.1111/j.1471-4159.1985.tb04048.x. PMID 4031854.
- Baudier J, Glasser N, Haglid K, Gerard D (1984). "Purification, characterization and ion binding properties of human brain S100b protein". Biochim. Biophys. Acta 790 (2): 164–73. doi:10.1016/0167-4838(84)90220-6. PMID 6487634.
- Adams MD, Kerlavage AR, Fleischmann RD, et al. (1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature 377 (6547 Suppl): 3–174. PMID 7566098. http://www.columbia.edu/itc/biology/pollack/w4065/client_edit/readings/nature377_3.pdf.
- Schäfer BW, Wicki R, Engelkamp D, et al. (1995). "Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family". Genomics 25 (3): 638–43. doi:10.1016/0888-7543(95)80005-7. PMID 7759097.
- Reeves RH, Yao J, Crowley MR, et al. (1994). "Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice". Proc. Natl. Acad. Sci. U.S.A. 91 (12): 5359–63. doi:10.1073/pnas.91.12.5359. PMC 43994. PMID 8202493. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43994.
- Engelkamp D, Schäfer BW, Mattei MG, et al. (1993). "Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E". Proc. Natl. Acad. Sci. U.S.A. 90 (14): 6547–51. doi:10.1073/pnas.90.14.6547. PMC 46969. PMID 8341667. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46969.
- Peña LA, Brecher CW, Marshak DR (1997). "beta-Amyloid regulates gene expression of glial trophic substance S100 beta in C6 glioma and primary astrocyte cultures". Brain Res. Mol. Brain Res. 34 (1): 118–26. doi:10.1016/0169-328X(95)00145-I. PMID 8750867.
- Argandoña EG, Bengoetxea H, Lafuente JV (2009). "Physical exercise is required for environmental enrichment to offset the quantitative effects of dark-rearing on the S-100β astrocytic density in the rat visual cortex". Journal of Anatomy. 215 (2): 132–40. doi:10.1111/j.1469-7580.2009.01103.x. PMC 2740960. PMID 19500177. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2740960.
- Landar A, Caddell G, Chessher J, Zimmer DB (1997). "Identification of an S100A1/S100B target protein: phosphoglucomutase". Cell Calcium 20 (3): 279–85. doi:10.1016/S0143-4160(96)90033-0. PMID 8894274.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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