请输入您要查询的百科知识：

　

词条 Desmin
释义

  1. Structure

  2. Function

  3. Clinical significance

  4. References

  5. External links

{{Infobox_gene}}Desmin is a protein that in humans is encoded by the DES gene.[1][2] Desmin is a muscle-specific, type III[3] intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture.[4][5]

Structure

Desmin is a 53.5 kD protein composed of 470 amino acids.[6][7] There are three major domains to the desmin protein: a conserved alpha helix rod, a variable non alpha helix head, and a carboxy-terminal tail.[8] Desmin, as all intermediate filaments, shows no polarity when assembled.[8] The rod domain consists of 308 amino acids with parallel alpha helical coiled coil dimers and three linkers to disrupt it.[8] The rod domain connects to the head domain. The head domain 84 amino acids with many arginine, serine, and aromatic residues is important in filament assembly and dimer-dimer interactions.[8] The tail domain is responsible for the integration of filaments and interaction with proteins and organelles. Desmin is only expressed in vertebrates, however homologous proteins are found in many organisms.[8] Desmin is a subunit of intermediate filaments in cardiac muscle, skeletal muscle and smooth muscle tissue.[9] In cardiac muscle, desmin is present in Z-discs and intercalated discs. Desmin has been shown to interact with desmoplakin[10] and αB-crystallin.[11]

Function

Desmin was first described in 1976,[12] first purified in 1977,[13] the gene was cloned in 1989,[2] and the first knockout mouse was created in 1996.[14] The function of desmin has been deduced through studies in knockout mice. Desmin is one of the earliest protein markers for muscle tissue in embryogenesis as it is detected in the somites.[8] Although it is present early in the development of muscle cells, it is only expressed at low levels, and increases as the cell nears terminal differentiation. A similar protein, vimentin, is present in higher amounts during embryogenesis while desmin is present in higher amounts after differentiation. This suggests that there may be some interaction between the two in determining muscle cell differentiation. However desmin knockout mice develop normally and only experience defects later in life.[9] Since desmin is expressed at a low level during differentiation another protein may be able to compensate for desmin's function early in development but not later on.[15]

In adult desmin-null mice, hearts from 10 wk-old animals showed drastic alterations in muscle architecture, including a misalignment of myofibrils and disorganization and swelling of mitochondria; findings that were more severe in cardiac relative to skeletal muscle. Cardiac tissue also exhibited progressive necrosis and calcification of the myocardium.[16] A separate study examined this in more detail in cardiac tissue and found that murine hearts lacking desmin developed hypertrophic cardiomyopathy and chamber dilation combined with systolic dysfunction.[17] In adult muscle, desmin forms a scaffold around the Z-disk of the sarcomere and connects the Z-disk to the subsarcolemmal cytoskeleton.[18] It links the myofibrils laterally by connecting the Z-disks.[8] Through its connection to the sarcomere, desmin connects the contractile apparatus to the cell nucleus, mitochondria, and post-synaptic areas of motor endplates.[8] These connections maintain the structural and mechanical integrity of the cell during contraction while also helping in force transmission and longitudinal load bearing.[18][19]

In human heart failure, desmin expression is upregulated, which has been hyopthesized to be a defense mechanism in an attempt to maintain normal sarcomere alignment amidst disease pathogenesis.[20] There is some evidence that desmin may also connect the sarcomere to the extracellular matrix (ECM) through desmosomes which could be important in signalling between the ECM and the sarcomere which could regulate muscle contraction and movement.[19] Finally, desmin may be important in mitochondria function. When desmin is not functioning properly there is improper mitochondrial distribution, number, morphology and function.[21][22] Since desmin links the mitochondria to the sarcomere it may transmit information about contractions and energy need and through this regulate the aerobic respiration rate of the muscle cell.

Clinical significance

Desmin-related myofibrillar myopathy (DRM or desminopathy) is a subgroup of the myofibrillar myopathy diseases and is the result of a mutation in the gene that codes for desmin which prevents it from forming protein filaments, and rather, forms aggregates of desmin and other proteins throughout the cell.[4][8] Desmin (DES) mutations have been associated with restrictive, dilated [23], idiopathic [24][25], arrhythmogenic [26][27][28] and non-compaction cardimyopathy.[29] Some of these DES mutations cause an aggregation of desmin within the cytoplasm.[30][31]A mutation p.A120D was discovered in a family, where several members had sudden cardiac death.[32] In addition, DES mutations cause frequently cardiac conduction diseases [33].

Desmin has been evaluated for role in assessing the depth of invasion of urothelial carcinoma in TURBT specimens.[34]

References

1. ^{{cite journal | vauthors = Muñoz-Mármol AM, Strasser G, Isamat M, Coulombe PA, Yang Y, Roca X, Vela E, Mate JL, Coll J, Fernández-Figueras MT, Navas-Palacios JJ, Ariza A, Fuchs E | title = A dysfunctional desmin mutation in a patient with severe generalized myopathy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 19 | pages = 11312–7 | date = September 1998 | pmid = 9736733 | pmc = 21639 | doi = 10.1073/pnas.95.19.11312 }}
2. ^1 {{cite journal | vauthors = Li ZL, Lilienbaum A, Butler-Browne G, Paulin D | title = Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development | journal = Gene | volume = 78 | issue = 2 | pages = 243–54 | date = May 1989 | pmid = 2673923 | doi = 10.1016/0378-1119(89)90227-8 }}
3. ^The Human Protein Atlas. Proteinatlas.org. Retrieved on 2013-07-29.
4. ^1 {{cite journal | vauthors = Brodehl A, Gaertner-Rommel A, Milting H | title = Molecular insights into cardiomyopathies associated with desmin (DES) mutations | journal = Biophysical Reviews | volume = 10 | issue = 4 | pages = 983–1006 | date = August 2018 | pmid = 29926427 | pmc = 6082305 | doi = 10.1007/s12551-018-0429-0 }}
5. ^{{cite journal | vauthors = Sequeira V, Nijenkamp LL, Regan JA, van der Velden J | title = The physiological role of cardiac cytoskeleton and its alterations in heart failure | journal = Biochimica et Biophysica Acta | volume = 1838 | issue = 2 | pages = 700–22 | date = February 2014 | pmid = 23860255 | doi = 10.1016/j.bbamem.2013.07.011 }}
6. ^{{cite web|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P17661 | title = Mass spectrometry characterization of human DES at COPaKB }}
7. ^{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
8. ^1 2 3 4 5 6 7 8 {{cite journal | vauthors = Bär H, Strelkov SV, Sjöberg G, Aebi U, Herrmann H | title = The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation? | journal = Journal of Structural Biology | volume = 148 | issue = 2 | pages = 137–52 | date = November 2004 | pmid = 15477095 | doi = 10.1016/j.jsb.2004.04.003 }}
9. ^1 {{cite journal | vauthors = Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D | title = Desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion of skeletal muscle | journal = The Journal of Cell Biology | volume = 139 | issue = 1 | pages = 129–44 | date = October 1997 | pmid = 9314534 | pmc = 2139820 | doi = 10.1083/jcb.139.1.129 }}
10. ^{{cite journal | vauthors = Meng JJ, Bornslaeger EA, Green KJ, Steinert PM, Ip W | title = Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments | journal = The Journal of Biological Chemistry | volume = 272 | issue = 34 | pages = 21495–503 | date = August 1997 | pmid = 9261168 | doi = 10.1074/jbc.272.34.21495 }}
11. ^{{cite journal | vauthors = Bennardini F, Wrzosek A, Chiesi M | title = Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments | journal = Circulation Research | volume = 71 | issue = 2 | pages = 288–94 | date = August 1992 | pmid = 1628387 | doi = 10.1161/01.res.71.2.288 }}
12. ^{{cite journal | vauthors = Lazarides E, Hubbard BD | title = Immunological characterization of the subunit of the 100 A filaments from muscle cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 12 | pages = 4344–8 | date = December 1976 | pmid = 1069986 | pmc = 431448 | doi = 10.1073/pnas.73.12.4344 }}
13. ^{{cite journal | vauthors = Izant JG, Lazarides E | title = Invariance and heterogeneity in the major structural and regulatory proteins of chick muscle cells revealed by two-dimensional gel electrophoresis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 74 | issue = 4 | pages = 1450–4 | date = April 1977 | pmid = 266185 | pmc = 430794 | doi = 10.1073/pnas.74.4.1450 }}
14. ^{{cite journal | vauthors = Costa ML, Escaleira R, Cataldo A, Oliveira F, Mermelstein CS | title = Desmin: molecular interactions and putative functions of the muscle intermediate filament protein | journal = Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas | volume = 37 | issue = 12 | pages = 1819–30 | date = December 2004 | pmid = 15558188 | doi = 10.1590/S0100-879X2004001200007 }}
15. ^{{cite web | url = http://www.cbil.upenn.edu/MTIR/dys-toc.html | title = Dystrophin | date = 1997-03-16 | access-date=2010-06-28 | work = Catalogue of Regulatory Elements | author = Stoeckert C | publisher = University of Pennsylvania }}
16. ^{{cite journal | vauthors = Milner DJ, Weitzer G, Tran D, Bradley A, Capetanaki Y | title = Disruption of muscle architecture and myocardial degeneration in mice lacking desmin | journal = The Journal of Cell Biology | volume = 134 | issue = 5 | pages = 1255–70 | date = September 1996 | pmid = 8794866 | pmc = 2120972 | doi = 10.1083/jcb.134.5.1255 }}
17. ^{{cite journal | vauthors = Milner DJ, Taffet GE, Wang X, Pham T, Tamura T, Hartley C, Gerdes AM, Capetanaki Y | title = The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function | journal = Journal of Molecular and Cellular Cardiology | volume = 31 | issue = 11 | pages = 2063–76 | date = November 1999 | pmid = 10591032 | doi = 10.1006/jmcc.1999.1037 }}
18. ^1 {{cite journal | vauthors = Paulin D, Li Z | title = Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle | journal = Experimental Cell Research | volume = 301 | issue = 1 | pages = 1–7 | date = November 2004 | pmid = 15501438 | doi = 10.1016/j.yexcr.2004.08.004 }}
19. ^1 {{cite journal | vauthors = Shah SB, Davis J, Weisleder N, Kostavassili I, McCulloch AD, Ralston E, Capetanaki Y, Lieber RL | title = Structural and functional roles of desmin in mouse skeletal muscle during passive deformation | journal = Biophysical Journal | volume = 86 | issue = 5 | pages = 2993–3008 | date = May 2004 | pmid = 15111414 | pmc = 1304166 | doi = 10.1016/S0006-3495(04)74349-0 }}
20. ^{{cite journal | vauthors = Heling A, Zimmermann R, Kostin S, Maeno Y, Hein S, Devaux B, Bauer E, Klövekorn WP, Schlepper M, Schaper W, Schaper J | title = Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium | journal = Circulation Research | volume = 86 | issue = 8 | pages = 846–53 | date = April 2000 | pmid = 10785506 | doi = 10.1161/01.res.86.8.846 }}
21. ^{{cite journal | vauthors = Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y | title = Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. | journal = Journal of Cell Biology | volume = 150 | issue = 6 | pages = 1283–1298 | year = 2000 | doi = 10.1083/jcb.150.6.1283 | citeseerx = 10.1.1.273.9903 }}
22. ^{{cite journal | vauthors = Goldfarb LG, Vicart P, Goebel HH, Dalakas MC | title = Desmin myopathy | journal = Brain | volume = 127 | issue = Pt 4 | pages = 723–34 | date = April 2004 | pmid = 14724127 | doi = 10.1093/brain/awh033 }}
23. ^{{cite journal | vauthors = Brodehl A, Dieding M, Biere N, Unger A, Klauke B, Walhorn V, Gummert J, Schulz U, Linke WA, Gerull B, Vorgert M, Anselmetti D, Milting H | title = Functional characterization of the novel DES mutation p.L136P associated with dilated cardiomyopathy reveals a dominant filament assembly defect | journal = Journal of Molecular and Cellular Cardiology | volume = 91 | pages = 207–14 | date = February 2016 | pmid = 26724190 | doi = 10.1016/j.yjmcc.2015.12.015 }}
24. ^{{cite journal | vauthors = Li D, Tapscoft T, Gonzalez O, Burch PE, Quiñones MA, Zoghbi WA, Hill R, Bachinski LL, Mann DL, Roberts R | title = Desmin mutation responsible for idiopathic dilated cardiomyopathy | journal = Circulation | volume = 100 | issue = 5 | pages = 461–4 | date = August 1999 | pmid = 10430757 | doi = 10.1161/01.cir.100.5.461 | authorlink6 = William Zoghbi }}
25. ^{{cite journal | vauthors = Goldfarb LG, Park KY, Cervenáková L, Gorokhova S, Lee HS, Vasconcelos O, Nagle JW, Semino-Mora C, Sivakumar K, Dalakas MC | title = Missense mutations in desmin associated with familial cardiac and skeletal myopathy | journal = Nature Genetics | volume = 19 | issue = 4 | pages = 402–3 | date = August 1998 | pmid = 9697706 | doi = 10.1038/1300 }}
26. ^{{cite journal | vauthors = Bermúdez-Jiménez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, Milting H, Abril BÁ, Álvarez M, López-Fernández S, García-Giustiniani D, Monserrat L, Tercedor L, Jiménez-Jáimez J | title = Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia | journal = Circulation | volume = 137 | issue = 15 | pages = 1595–1610 | date = April 2018 | pmid = 29212896 | doi = 10.1161/CIRCULATIONAHA.117.028719 }}
27. ^{{cite journal | vauthors = Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H | title = De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy | journal = Human Molecular Genetics | volume = 19 | issue = 23 | pages = 4595–607 | date = December 2010 | pmid = 20829228 | doi = 10.1093/hmg/ddq387 }}
28. ^{{cite journal | vauthors = Lorenzon A, Beffagna G, Bauce B, De Bortoli M, Li Mura IE, Calore M, Dazzo E, Basso C, Nava A, Thiene G, Rampazzo A | title = Desmin mutations and arrhythmogenic right ventricular cardiomyopathy | journal = The American Journal of Cardiology | volume = 111 | issue = 3 | pages = 400–5 | date = February 2013 | pmid = 23168288 | pmc = 3554957 | doi = 10.1016/j.amjcard.2012.10.017 }}
29. ^{{cite journal | vauthors = Marakhonov AV, Brodehl A, Myasnikov RP, Sparber PA, Kiseleva AV, Kulikova OV, Meshkov AN, Zharikova AA, Koretsky SN, Kharlap MS, Stanasiuk C, Mershina EA, Sinitsyn VE, Shevchenko AO, Mozheyko NP, Drapkina OM, Boytsov SA, Milting H, Skoblov MY | title = Non-compaction cardiomyopathy is caused by a novel in-frame desmin (DES) deletion mutation within the 1A coiled-coil rod segment leading to a severe filament assembly defect | journal = Human Mutation | date = March 2019 | pmid = 30908796 | doi = 10.1002/humu.23747 }}
30. ^{{cite journal | vauthors = Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H | title = Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants | journal = The Journal of Biological Chemistry | volume = 287 | issue = 19 | pages = 16047–57 | date = May 2012 | pmid = 22403400 | pmc = 3346104 | doi = 10.1074/jbc.M111.313841 }}
31. ^{{cite journal | vauthors = Brodehl A, Ebbinghaus H, Gaertner-Rommel A, Stanasiuk C, Klauke B, Milting H | title = Functional analysis of DES-p.L398P and RBM20-p.R636C | journal = Genetics in Medicine | date = September 2018 | pmid = 30262925 | doi = 10.1038/s41436-018-0291-2 }}
32. ^{{cite journal | vauthors = Brodehl A, Dieding M, Klauke B, Dec E, Madaan S, Huang T, Gargus J, Fatima A, Saric T, Cakar H, Walhorn V, Tönsing K, Skrzipczyk T, Cebulla R, Gerdes D, Schulz U, Gummert J, Svendsen JH, Olesen MS, Anselmetti D, Christensen AH, Kimonis V, Milting H | title = The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death | journal = Circulation. Cardiovascular Genetics | volume = 6 | issue = 6 | pages = 615–23 | date = December 2013 | pmid = 24200904 | doi = 10.1161/CIRCGENETICS.113.000103 }}
33. ^{{cite journal | vauthors = Schirmer I, Dieding M, Klauke B, Brodehl A, Gaertner-Rommel A, Walhorn V, Gummert J, Schulz U, Paluszkiewicz L, Anselmetti D, Milting H | title = A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy | journal = Molecular Genetics & Genomic Medicine | volume = 6 | issue = 2 | pages = 288–293 | date = March 2018 | pmid = 29274115 | pmc = 5902401 | doi = 10.1002/mgg3.358 }}
34. ^Saha K, Saha A, Datta C, Chatterjee U, Ray S, Bera M. Does desmin immunohistochemistry have a role in assessing stage of urothelial carcinoma in transurethral resection of bladder tumor specimens? Clin Cancer Investig J 2014;3(6):502-7.DOI: 10.4103/2278-0513.142634

External links

  • [https://www.ncbi.nlm.nih.gov/books/NBK1499/ GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy]
  • {{MeshName|Desmin}}
  • LOVD mutation database: DES
{{Cytoskeletal Proteins}}{{Muscle tissue}}{{Tumor markers}}

1 : Tumor markers
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。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/12 1:51:32