| 词条 | Dystrophin |
| 释义 |
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 (DAPC). Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. The DMD gene, encoding the dystrophin protein, is one of the longest human genes known, covering 2.3 megabases (0.08% of the human genome) at locus Xp21. The primary transcript in muscle measures about 2,100 kilobases and takes 16 hours to transcribe;[1] the mature mRNA measures 14.0 kilobases.[2] The 79-exon muscle transcript[3] codes for a protein of 3685 amino acid residues.[4] FunctionDystrophin is a protein located between the sarcolemma and the outermost layer of myofilaments in the muscle fiber (myofiber). It is a cohesive protein, linking actin filaments to other support proteins that reside on the inside surface of each muscle fiber's plasma membrane (sarcolemma). These support proteins on the inside surface of the sarcolemma in turn links to two other consecutive proteins for a total of three linking proteins. The final linking protein is attached to the fibrous endomysium of the entire muscle fiber. Dystrophin supports muscle fiber strength, and the absence of dystrophin reduces muscle stiffness, increases sarcolemmal deformability, and compromises the mechanical stability of costameres and their connections to nearby myofibrils. This has been shown in recent studies where biomechanical properties of the sarcolemma and its links through costameres to the contractile apparatus were measured,[5] and helps to prevent muscle fiber injury. Movement of thin filaments (actin) creates a pulling force on the extracellular connective tissue that eventually becomes the tendon of the muscle. The dystrophin associated protein complex also helps scaffold various signalling and channel proteins, implicating the DAPC in regulation of signalling processes.[6] PathologyDystrophin deficiency has been definitively established as one of the root causes of the general class of myopathies collectively referred to as muscular dystrophy. The large cytosolic protein was first identified in 1987 by Louis M. Kunkel,[7] after concurrent works by Kunkel and Robert G. Worton to characterize the mutated gene that causes Duchenne muscular dystrophy (DMD).[8][9] Normal skeletal muscle tissue contains only small amounts of dystrophin (about 0.002% of total muscle protein),[10] but its absence (or abnormal expression) leads to the development of a severe and currently incurable constellation of symptoms most readily characterized by several aberrant intracellular signaling pathways that ultimately yield pronounced myofiber necrosis as well as progressive muscle weakness and fatigability. Most DMD patients become wheelchair-dependent early in life, and the gradual development of cardiac hypertrophy—a result of severe myocardial fibrosis—typically results in premature death in the first two or three decades of life. Variants (mutations) in the DMD gene that lead to the production of too little or a defective, internally shortened but partially functional dystrophin protein, result in a display of a much milder dystrophic phenotype in affected patients, resulting in the disease known as Becker's muscular dystrophy (BMD). In some cases, the patient's phenotype is such that experts may decide differently on whether a patient should be diagnosed with DMD or BMD. The theory currently most commonly used to predict whether a variant will result in a DMD or BMD phenotype, is the reading frame rule.[11] 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.[12] InteractionsDystrophin has been shown to interact with:
Neanderthal admixtureA variant of the DMD gene, which is on the X chromosome, named B006, appears to be an introgression from a Neanderthal-modern human mating.[18] References1. ^{{cite journal | vauthors = Tennyson CN, Klamut HJ, Worton RG | title = The human dystrophin gene requires 16 hours to be transcribed and is cotranscriptionally spliced | journal = Nature Genetics | volume = 9 | issue = 2 | pages = 184–90 | date = February 1995 | pmid = 7719347 | doi = 10.1038/ng0295-184 }} 2. ^[https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NM_000109.2 NCBI Sequence Viewer v2.0] 3. ^Strachan T and Read AP, 1999. Human molecular genetics, BIOS Scientific, New York, USA 4. ^[https://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_000100.2 NCBI Sequence Viewer v2.0] 5. ^{{cite journal | vauthors = García-Pelagio KP, Bloch RJ, Ortega A, González-Serratos H | title = Biomechanics of the sarcolemma and costameres in single skeletal muscle fibers from normal and dystrophin-null mice | journal = Journal of Muscle Research and Cell Motility | volume = 31 | issue = 5–6 | pages = 323–36 | date = March 2011 | pmid = 21312057 | pmc = 4326082 | doi = 10.1007/s10974-011-9238-9 }} 6. ^{{cite journal | vauthors = Constantin B | title = Dystrophin complex functions as a scaffold for signalling proteins | journal = Biochimica et Biophysica Acta | volume = 1838 | issue = 2 | pages = 635–42 | date = February 2014 | pmid = 24021238 | doi = 10.1016/j.bbamem.2013.08.023 }} 7. ^{{cite journal | vauthors = Hoffman EP, Brown RH, Kunkel LM | title = Dystrophin: the protein product of the Duchenne muscular dystrophy locus | journal = Cell | volume = 51 | issue = 6 | pages = 919–28 | date = December 1987 | pmid = 3319190 | doi = 10.1016/0092-8674(87)90579-4 }} 8. ^{{cite journal | vauthors = Monaco AP, Neve RL, Colletti-Feener C, Bertelson CJ, Kurnit DM, Kunkel LM | title = Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene | journal = Nature | volume = 323 | issue = 6089 | pages = 646–50 | year = 1986 | pmid = 3773991 | doi = 10.1038/323646a0 | bibcode = 1986Natur.323..646M }} 9. ^{{cite journal | vauthors = Burghes AH, Logan C, Hu X, Belfall B, Worton RG, Ray PN | title = A cDNA clone from the Duchenne/Becker muscular dystrophy gene | journal = Nature | volume = 328 | issue = 6129 | pages = 434–7 | date = 1987 | pmid = 3614347 | doi = 10.1038/328434a0 }} 10. ^{{cite journal | vauthors = Hoffman EP, Brown RH, Kunkel LM | title = Dystrophin: the protein product of the Duchenne muscular dystrophy locus | journal = Cell | volume = 51 | issue = 6 | pages = 919–28 | date = December 1987 | pmid = 3319190 | doi = 10.1016/0092-8674(87)90579-4 }} 11. ^{{cite journal | vauthors = Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT | title = Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule | journal = Muscle & Nerve | volume = 34 | issue = 2 | pages = 135–44 | date = August 2006 | pmid = 16770791 | doi = 10.1002/mus.20586 }} 12. ^{{cite journal | vauthors = Sharma P, Tran T, Stelmack GL, McNeill K, Gosens R, Mutawe MM, Unruh H, Gerthoffer WT, Halayko AJ | title = Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation | journal = American Journal of Physiology. Lung Cellular and Molecular Physiology | volume = 294 | issue = 1 | pages = L57–68 | date = January 2008 | pmid = 17993586 | doi = 10.1152/ajplung.00378.2007 }} 13. ^{{cite journal | vauthors = Sadoulet-Puccio HM, Rajala M, Kunkel LM | title = Dystrobrevin and dystrophin: an interaction through coiled-coil motifs | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 23 | pages = 12413–8 | date = November 1997 | pmid = 9356463 | pmc = 24974 | doi = 10.1073/pnas.94.23.12413 | bibcode = 1997PNAS...9412413S }} 14. ^{{cite journal | vauthors = Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM | title = The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives | journal = The Journal of Biological Chemistry | volume = 271 | issue = 5 | pages = 2724–30 | date = February 1996 | pmid = 8576247 | doi = 10.1074/jbc.271.5.2724 }} 15. ^{{cite journal | vauthors = Yang B, Jung D, Rafael JA, Chamberlain JS, Campbell KP | title = Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin | journal = The Journal of Biological Chemistry | volume = 270 | issue = 10 | pages = 4975–8 | date = March 1995 | pmid = 7890602 | doi = 10.1074/jbc.270.10.4975 }} 16. ^{{cite journal | vauthors = Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC | title = Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins | journal = The Journal of Neuroscience | volume = 18 | issue = 1 | pages = 128–37 | date = January 1998 | pmid = 9412493 | doi = }} 17. ^{{cite journal | vauthors = Ahn AH, Kunkel LM | title = Syntrophin binds to an alternatively spliced exon of dystrophin | journal = The Journal of Cell Biology | volume = 128 | issue = 3 | pages = 363–71 | date = February 1995 | pmid = 7844150 | pmc = 2120343 | doi = 10.1083/jcb.128.3.363 }} 18. ^{{cite web|url=http://blogs.discovermagazine.com/gnxp/2011/01/neandertal-admixture-revisiting-results-after-shaken-priors/|work=Discover Magazine|title=Neandertal admixture, revisiting results after shaken priors|last=Khan|first=Razib | name-list-format = vanc |date=January 25, 2011|access-date=March 27, 2013}} Further reading{{refbegin | 2}}
External links
3 : Cytoskeleton|Muscular dystrophy|Cell adhesion proteins |
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。