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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/07 22:32:00」(JST)

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Desmin is a protein that in humans is encoded by the DES gene.^[1]^[2]

Desmin is a type III^[3] intermediate filament found near the Z line in sarcomeres. It was first described in 1976,^[4] first purified in 1977,^[5] the gene was cloned in 1989,^[2] and the first knockout mouse was created in 1996.^[6] Desmin is only expressed in vertebrates, however homologous proteins are found in many organisms.^[7] It is a 52kD protein that is a subunit of intermediate filaments in skeletal muscle tissue, smooth muscle tissue, and cardiac muscle tissue.^[8]

Putative functions

The function of desmin has been deduced through studies in knockout mice, but the underlying mechanism of its action is not known. These possibilities may be the result of interactions with other proteins and not desmin itself. More research needs to be done on desmin's expression and interactions in the muscle cell in order to determine its exact function.

Desmin is one of the earliest protein markers for muscle tissue in embryogenesis as it is detected in the somites.^[7] 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.^[8] 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.^[9]

Desmin is also important in muscle cell architecture and structure since it connects many components of the cytoplasm. The sarcomere is a component of muscle cells composed of actin and myosin motor proteins which allow the cell to contract. Desmin forms a scaffold around the Z-disk of the sarcomere and connects the Z-disk to the subsarcolemmal cytoskeleton (the cytoplasmic part of the muscle cell plasma membrane).^[10] It links the myofibrils laterally by connecting the Z-disks.^[7] Through its connection to the sarcomere Desmin connects the contractile apparatus to the cell nucleus, mitochondria, and post-synaptic areas of motor endplates.^[7] These connections maintain the structural and mechanical integrity of the cell during contraction while also helping in force transmission and longitudinal load bearing.^[10]^[11] 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.^[11]

Finally, desmin may be important in mitochondria function. When desmin is not functioning properly there is improper mitochondrial distribution, number, morphology and function.^[12] 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.

Knockout phenotype

When the gene for desmin is knocked out it is no longer able to function properly. Mice with the desmin knockout gene develop normally and are fertile, however soon after birth they begin to show defects in skeletal, smooth and cardiac muscle; in particular the diaphragm and heart are affected.^[8] The mice without desmin are weaker and fatigue more easily than wild type mice ^[13] ^[8] but the muscle fibers are less likely to be damaged during contraction ^[14] Mice without desmin also have impaired mitochondrial function.

Associated diseases

Main article: Desmin-related myofibrillar myopathy

Desmin-related 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, instead forming aggregates of desmin and other proteins throughout the cell.^[7] Recently, mutations were identified in patients suffered by an arrhythmogenic right ventricular cardiomyopathy (ARVC). ^[15] Some of these DES mutations like p.N116S or p.E114del cause an aggregation of desmin within the cytoplasma. ^[16] Recently, a novel mutation p.A120D was discovered in family where several members had a sudden cardiac death. ^[17] It is also associated with Sarcoma botryoides (rhabdomyosarcoma variant) - a vaginal malignancy composed of spindle-shaped cells that affects girls < 4 years of age.

Structure

There are three major domains to this protein: a conserved alpha helix rod, a variable non alpha helix head, and a carboxy-terminal tail.^[7] Desmin, as all intermediate filaments, shows no polarity when assembled.^[7] The rod domain consists of 308 amino acids with parallel alpha helical coiled coil dimers and three linkers to disrupt it.^[7] 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.^[7] The tail domain is responsible for the integration of filaments and interaction with proteins and organelles.

Interactions

Desmin has been shown to interact with Desmoplakin.^[18]

References

^ 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 (September 1998). "A dysfunctional desmin mutation in a patient with severe generalized myopathy". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11312–7. doi:10.1073/pnas.95.19.11312. PMC 21639. PMID 9736733.
^ ^a ^b Li ZL, Lilienbaum A, Butler-Browne G, Paulin D (May 1989). "Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development". Gene 78 (2): 243–54. doi:10.1016/0378-1119(89)90227-8. PMID 2673923.
^ The Human Protein Atlas. Proteinatlas.org. Retrieved on 2013-07-29.
^ Lazarides E, Hubbard BD (December 1976). "Immunological characterization of the subunit of the 100 A filaments from muscle cells". Proc. Natl. Acad. Sci. U.S.A. 73 (12): 4344–8. doi:10.1073/pnas.73.12.4344. PMC 431448. PMID 1069986.
^ Izant JG, Lazarides E (April 1977). "Invariance and heterogeneity in the major structural and regulatory proteins of chick muscle cells revealed by two-dimensional gel electrophoresis". Proc. Natl. Acad. Sci. U.S.A. 74 (4): 1450–4. doi:10.1073/pnas.74.4.1450. PMC 430794. PMID 266185.
^ Costa ML, Escaleira R, Cataldo A, Oliveira F, Mermelstein CS (December 2004). "Desmin: molecular interactions and putative functions of the muscle intermediate filament protein". Braz. J. Med. Biol. Res. 37 (12): 1819–30. doi:10.1590/S0100-879X2004001200007. PMID 15558188.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Bär H, Strelkov SV, Sjöberg G, Aebi U, Herrmann H (November 2004). "The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation?". J. Struct. Biol. 148 (2): 137–52. doi:10.1016/j.jsb.2004.04.003. PMID 15477095.
^ ^a ^b ^c ^d Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D (October 1997). "Desmin Is Essential for the Tensile Strength and Integrity of Myofibrils but Not for Myogenic Commitment, Differentiation, and Fusion of Skeletal Muscle". J. Cell Biol. 139 (1): 129–44. doi:10.1083/jcb.139.1.129. PMC 2139820. PMID 9314534.
^ Stoeckert C (1997-03-16). "Dystrophin". Catalogue of Regulatory Elements. University of Pennsylvania. Retrieved 2010-06-28.
^ ^a ^b Paulin D, Li Z (November 2004). "Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle". Exp. Cell Res. 301 (1): 1–7. doi:10.1016/j.yexcr.2004.08.004. PMID 15501438.
^ ^a ^b Shah SB, Davis J, Weisleder N, Kostavassili I, McCulloch AD, Ralston E, Capetanaki Y, Lieber RL (May 2004). "Structural and Functional Roles of Desmin in Mouse Skeletal Muscle during Passive Deformation". Biophys. J. 86 (5): 2993–3008. doi:10.1016/S0006-3495(04)74349-0. PMC 1304166. PMID 15111414.
^ Goldfarb LG, Vicart P, Goebel HH, Dalakas MC (April 2004). "Desmin myopathy". Brain 127 (Pt 4): 723–34. doi:10.1093/brain/awh033. PMID 14724127.
^ K Garcia-Pelagio, R Bloch, H Gonzáles-Serratos (2010). "Modeling the Cell Muscle Membrane from Normal and Desmin or Dystrophin null Mice as an Elastic System". AIP Conf. Proc. 1310 (1): 68–72.
^ Sam M, Shah S, Fridén J, Milner DJ, Capetanaki Y, Lieber RL (October 2000). "Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles". Am. J. Physiol., Cell Physiol. 279 (4): C1116–22. PMID 11003592.
^ 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. De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet. 2010 Dec 1;19(23):4595-607. doi: 10.1093/hmg/ddq387. Epub 2010 Sep 9.
^ 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. Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants. J Biol Chem. 2012 May 4;287(19):16047-57. doi: 10.1074/jbc.M111.313841. Epub 2012 Mar 8. PMID: 22403400
^ 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.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. The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death. Circ Cardiovasc Genet. 2013 Dec;6(6):615-23. doi:10.1161/CIRCGENETICS.113.000103
^ Meng JJ, Bornslaeger EA, Green KJ, Steinert PM, Ip W (August 1997). "Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments". J. Biol. Chem. 272 (34): 21495–503. doi:10.1074/jbc.272.34.21495. PMID 9261168.

External links

GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy
Desmin at the US National Library of Medicine Medical Subject Headings (MeSH)
LOVD mutation database: DES

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. デスモイド腫瘍：疫学、危険因子、分子学的病因、臨床症状、診断、および局所療法 desmoid tumors epidemiology risk factors molecular pathogenesis clinical presentation diagnosis and local therapy
2. 心疾患関連する遺伝性症候群 inherited syndromes associated with cardiac disease
3. 拡張型心筋症の遺伝学 genetics of dilated cardiomyopathy
4. 小児および思春期の横紋筋肉腫：疫学、病理、および分子学的病因 rhabdomyosarcoma in childhood and adolescence epidemiology pathology and molecular pathogenesis
5. GISTを含む消化管間葉系腫瘍の疫学、分類、臨床像、予後の特徴、および診断方法 epidemiology classification clinical presentation prognostic features and diagnostic work up of gastrointestinal mesenchymal neoplasms including gist

English Journal

Nesprin‑1 has key roles in the process of mesenchymal stem cell differentiation into cardiomyocyte‑like cells in vivo and in vitro.

Yang W, Zheng H, Wang Y, Lian F, Hu Z, Xue S.
Molecular medicine reports.Mol Med Rep.2015 Jan;11(1):133-42. doi: 10.3892/mmr.2014.2754. Epub 2014 Oct 23.
The aim of the present study was to investigate the expression of nesprin‑1 protein in MSCs and its effects on the differentiation of rat bone‑marrow mesenchymal stem cells (MSCs). Surface‑associated antigens of MSCs were detected by flow cytometry. MSC differentiation was induced by treatment
PMID 25339194

Isolation and passage of muscle-derived stem cells from the rat penile corpora cavernosa and induction of differentiation into smooth muscle cells.

Xu LJ1, Xue BX, Chen D, Gao J, Yang DR, Sun CY, Cui Y, Shan YX.
Cytotechnology.Cytotechnology.2014 Dec;66(6):987-94. doi: 10.1007/s10616-013-9651-6. Epub 2013 Nov 19.
This study treated the isolation and passage of muscle-derived stem cells (MDSCs) from rat penile corpora cavernosa, detection of stem cell marker expression, observation of their self-renewal and continuous proliferation, and demonstration of their potential to differentiate into smooth muscle cell
PMID 24242826

Disruption of both nesprin 1 and desmin results in nuclear anchorage defects and fibrosis in skeletal muscle.

Chapman MA1, Zhang J2, Banerjee I2, Guo LT3, Zhang Z4, Shelton GD3, Ouyang K5, Lieber RL6, Chen J7.
Human molecular genetics.Hum Mol Genet.2014 Nov 15;23(22):5879-92. doi: 10.1093/hmg/ddu310. Epub 2014 Jun 18.
Proper localization and anchorage of nuclei within skeletal muscle is critical for cellular function. Alterations in nuclear anchoring proteins modify a number of cellular functions including mechanotransduction, nuclear localization, chromatin positioning/compaction and overall organ function. In s
PMID 24943590

Japanese Journal

Medial Pterygoid initiated the Growth of the Mandible through Premature Muscle Contraction

Kikuchi Ryusuke,Yamamoto Masahito,Kitamura Kei [他]
Journal of hard tissue biology 23(2), 225-231, 2014-04
NAID 40020071328

胃glomus腫瘍の1切除例

熊本幸司,松本英一,藤井幸治,高橋幸二,宮原成樹,楠田司,KUMAMOTO Koji,MATSUMOTO Eiichi,FUJII Koji,TAKAHASHI Koji,MIYAHARA Shigeki,KUSUTA Tsukasa
三重医学 57(1), 11-15, 2014-03-25
… ．上部消化管内視鏡検査にて胃前庭部に粘膜下腫瘍および同腫瘍からの出血を認めた．緊急内視鏡的止血術を施行し，一旦止血が得られたが，後日再度同腫瘍からの出血を認めたため，緊急にて胃部分切除術を施行した．病理所見は，免疫染色でc-Kit，CD 34，S 100，desmin，Chromograninはいずれも陰性，SMAのみ陽性であり，glomus腫瘍と診断された．胃に発生するglomus腫瘍は比較的まれであるため，文献的考察を加え報告する． …
NAID 120005425389

Calponin Expression in Renal Tubulointerstitial Fibrosis Induced in Rats by Cisplatin

YUASA Takahiro,YANO Ryo,IZAWA Takeshi,KUWAMURA Mitsuru,YAMATE Jyoji
Journal of Toxicologic Pathology, 2014
… Myofibroblasts play important roles in progression of the fibrosis and are characterized by expressions of various cytoskeletons such as vimentin, desmin and α-smooth muscle actin (α-SMA). … Calponin-expressing interstitial cells increased with fibrosis and reacted simultaneously to vimentin or α-SMA (a marker of well-differentiated myofibroblasts) but not desmin or Thy-1 (a marker of myofibroblasts at the early stage). …
NAID 130003391344

Related Pictures

★リンクテーブル★

リンク元	「粘膜下腫瘍」「デスミン」

「粘膜下腫瘍」

Desmin
Identifiers
Symbols	DES (; CSM1; CSM2)
External IDs	OMIM: 125660 MGI: 94885 HomoloGene: 56469 GeneCards: DES Gene
Gene Ontology
Molecular function	• structural constituent of cytoskeleton; • protein binding; • cytoskeletal protein binding;
Cellular component	• cytosol; • intermediate filament; • fascia adherens; • Z disc; • neuromuscular junction; • sarcolemma;
Biological process	• muscle contraction; • cytoskeleton organization; • regulation of heart contraction; • muscle filament sliding;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: submucosal tumor
関: 消化管粘膜下腫瘍、胃粘膜下腫瘍

概念

主病変が粘膜下層以下に存在する隆起病変の総称

分類

胃

非上皮病変

間葉系腫瘍 gastrointestinal mesenchymal tumor GIMT

GIST：CD34(+), c-Kit(+)　　　→　　　粘膜下腫瘍の中で最多である。
筋原性腫瘍：平滑筋腫、平滑筋肉腫、類上皮平滑筋肉腫：smooth muscle actin(+), desmin(+)
神経原性腫瘍：神経鞘腫、神経線維腫：S-100(+)

上皮性病変

迷入膵
嚢胞
カルチノイド

炎症性病変

好酸球性肉芽腫

形態的特徴

Delle デレ
なだらかな陰影の移行(造影、X線透視)、なだらかな隆起の移行(内視鏡)
bridging fold(ヒダが腫瘤をよけない)
粘膜表面に異常は認められない(圧排が強くなれば何らかの影響はある、と思う)

参考

1.

http://www.cancernetwork.com/gastrointestinal-stromal-tumor/content/article/10162/35555

「デスミン」

　　[★]

英: desmin
関

臨床関連

消化管間質腫瘍(GIST)と平滑筋腫の鑑別に使える

[pmid9736733-1] 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 (September 1998). "A dysfunctional desmin mutation in a patient with severe generalized myopathy". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11312–7. doi:10.1073/pnas.95.19.11312. PMC 21639. PMID 9736733.

[pmid2673923-2] Li ZL, Lilienbaum A, Butler-Browne G, Paulin D (May 1989). "Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development". Gene 78 (2): 243–54. doi:10.1016/0378-1119(89)90227-8. PMID 2673923.

[3] The Human Protein Atlas. Proteinatlas.org. Retrieved on 2013-07-29.

[pmid1069986-4] Lazarides E, Hubbard BD (December 1976). "Immunological characterization of the subunit of the 100 A filaments from muscle cells". Proc. Natl. Acad. Sci. U.S.A. 73 (12): 4344–8. doi:10.1073/pnas.73.12.4344. PMC 431448. PMID 1069986.

[pmid266185-5] Izant JG, Lazarides E (April 1977). "Invariance and heterogeneity in the major structural and regulatory proteins of chick muscle cells revealed by two-dimensional gel electrophoresis". Proc. Natl. Acad. Sci. U.S.A. 74 (4): 1450–4. doi:10.1073/pnas.74.4.1450. PMC 430794. PMID 266185.

[Costa-6] Costa ML, Escaleira R, Cataldo A, Oliveira F, Mermelstein CS (December 2004). "Desmin: molecular interactions and putative functions of the muscle intermediate filament protein". Braz. J. Med. Biol. Res. 37 (12): 1819–30. doi:10.1590/S0100-879X2004001200007. PMID 15558188.

[Bar-7] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Bär H, Strelkov SV, Sjöberg G, Aebi U, Herrmann H (November 2004). "The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation?". J. Struct. Biol. 148 (2): 137–52. doi:10.1016/j.jsb.2004.04.003. PMID 15477095.

[Li-8] Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D (October 1997). "Desmin Is Essential for the Tensile Strength and Integrity of Myofibrils but Not for Myogenic Commitment, Differentiation, and Fusion of Skeletal Muscle". J. Cell Biol. 139 (1): 129–44. doi:10.1083/jcb.139.1.129. PMC 2139820. PMID 9314534.

[9] Stoeckert C (1997-03-16). "Dystrophin". Catalogue of Regulatory Elements. University of Pennsylvania. Retrieved 2010-06-28.

[Paulin-10] Paulin D, Li Z (November 2004). "Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle". Exp. Cell Res. 301 (1): 1–7. doi:10.1016/j.yexcr.2004.08.004. PMID 15501438.

[Shah-11] Shah SB, Davis J, Weisleder N, Kostavassili I, McCulloch AD, Ralston E, Capetanaki Y, Lieber RL (May 2004). "Structural and Functional Roles of Desmin in Mouse Skeletal Muscle during Passive Deformation". Biophys. J. 86 (5): 2993–3008. doi:10.1016/S0006-3495(04)74349-0. PMC 1304166. PMID 15111414.

[Goldfarb-12] Goldfarb LG, Vicart P, Goebel HH, Dalakas MC (April 2004). "Desmin myopathy". Brain 127 (Pt 4): 723–34. doi:10.1093/brain/awh033. PMID 14724127.

[13] K Garcia-Pelagio, R Bloch, H Gonzáles-Serratos (2010). "Modeling the Cell Muscle Membrane from Normal and Desmin or Dystrophin null Mice as an Elastic System". AIP Conf. Proc. 1310 (1): 68–72.

[14] Sam M, Shah S, Fridén J, Milner DJ, Capetanaki Y, Lieber RL (October 2000). "Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles". Am. J. Physiol., Cell Physiol. 279 (4): C1116–22. PMID 11003592.

[15] 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. De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet. 2010 Dec 1;19(23):4595-607. doi: 10.1093/hmg/ddq387. Epub 2010 Sep 9.

[16] 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. Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants. J Biol Chem. 2012 May 4;287(19):16047-57. doi: 10.1074/jbc.M111.313841. Epub 2012 Mar 8. PMID: 22403400

[17] 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.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. The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death. Circ Cardiovasc Genet. 2013 Dec;6(6):615-23. doi:10.1161/CIRCGENETICS.113.000103

[pmid9261168-18] Meng JJ, Bornslaeger EA, Green KJ, Steinert PM, Ip W (August 1997). "Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments". J. Biol. Chem. 272 (34): 21495–503. doi:10.1074/jbc.272.34.21495. PMID 9261168.

匿名

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案内

案内

desmin