Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex. Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere.
As of 2007, dystrophin is the longest gene known, covering 2.4 megabases (0.08% of the human genome) at locus Xp21. The primary transcript measures about 2,400 kilobases and takes 16 hours to transcribe, the mature mRNA measures 14.0 kilobases1. The 79 exons2 code for a protein of over 3500 amino acid residues.3
Pathology
Its deficiency is one of the root causes of muscular dystrophy. It was first identified in 1987 by Louis M. Kunkel 4, after the 1986 discovery of the mutated gene that causes Duchenne muscular dystrophy (DMD) 5.
Normal tissue contains small amounts of dystrophin (about 0.002% of total muscle protein), but its absence leads to both DMD and fibrosis, a condition of muscle hardening. A different mutation of the same gene causes defective dystrophin, leading to Becker's muscular dystrophy (BMD).
Though its role in airway smooth muscle is not well established recent research indicates that dystrophin along with other subunits of dystrophin glycoprotein complex is associated with phenotype maturation.6
References
- ^ NCBI Sequence Viewer v2.0
- ^ Strachan T and Read AP, 1999. Human molecular genetics, BIOS Scientific, New York, USA
- ^ NCBI Sequence Viewer v2.0
- ^ Hoffman E, Brown R, Kunkel L (1987). "Dystrophin: the protein product of the Duchenne muscular dystrophy locus". Cell 51 (6): 919–28. doi:10.1016/0092-8674(87)90579-4. PMID 3319190.
- ^ Monaco A, Neve R, Colletti-Feener C et al (1986). "Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene". Nature 323 (6089): 646–50. doi:10.1038/323646a0. PMID 3773991.
- ^ Sharma P, Tran T, Stelmack GL, et al (2008). "Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation". Am. J. Physiol. Lung Cell Mol. Physiol. 294 (1): L57–68. doi:10.1152/ajplung.00378.2007. PMID 17993586.
Further reading
- Roberts RG, Gardner RJ, Bobrow M (1994). "Searching for the 1 in 2,400,000: a review of dystrophin gene point mutations". Hum. Mutat. 4 (1): 1–11. doi:10.1002/humu.1380040102. PMID 7951253.
- Tinsley JM, Blake DJ, Zuellig RA, Davies KE (1994). "Increasing complexity of the dystrophin-associated protein complex". Proc. Natl. Acad. Sci. U.S.A. 91 (18): 8307–13. doi:10.1073/pnas.91.18.8307. PMID 8078878.
- Blake DJ, Weir A, Newey SE, Davies KE (2002). "Function and genetics of dystrophin and dystrophin-related proteins in muscle". Physiol. Rev. 82 (2): 291–329. doi:10.1152/physrev.00028.2001 (inactive 22 June 2008). PMID 11917091.
- Röper K, Gregory SL, Brown NH (2003). "The 'spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families". J. Cell. Sci. 115 (Pt 22): 4215–25. PMID 12376554.
- Muntoni F, Torelli S, Ferlini A (2003). "Dystrophin and mutations: one gene, several proteins, multiple phenotypes". Lancet neurology 2 (12): 731–40. doi:10.1016/S1474-4422(03)00585-4. PMID 14636778.
- Haenggi T, Fritschy JM (2006). "Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue". Cell. Mol. Life Sci. 63 (14): 1614–31. doi:10.1007/s00018-005-5461-0. PMID 16710609.
External links
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Proteins of the cytoskeleton |
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| Microfilaments |
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| Intermediate filaments |
type 1 and 2 ( Cytokeratin, type I, type II) - type 3 ( Desmin, GFAP, Peripherin, Vimentin) - type 4 ( Internexin, Nestin, Neurofilament, Synemin, Syncoilin) - type 5 ( Lamin A, B)
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| Microtubules |
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| Catenins |
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| Nonhuman |
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| Other |
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Histology: muscle tissue |
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| skeletal muscle/general |
epimysium, fascicle, perimysium, endomysium, muscle fiber ( intrafusal, extrafusal), myofibril
sarcomere (a, i, and h bands; z and m lines), myofilaments (thin filament/actin, thick filament/myosin, elastic filament/titin, nebulin), tropomyosin, troponin (T, C, I)
costamere (dystrophin, α,β-dystrobrevin, syncoilin, synemin/desmuslin, dysbindin, sarcoglycan, dystroglycan, sarcospan), desmin
neuromuscular junction, motor unit, muscle spindle, excitation-contraction coupling, sliding filament mechanism
myoblast, satellite cell, sarcoplasm, sarcolemma, sarcoplasmic reticulum, T-tubule
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| cardiac muscle |
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| smooth muscle |
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