Open Access Articles- Top Results for Plectin


External IDsOMIM601282 MGI1277961 HomoloGene384 ChEMBL: 1293240 GeneCards: PLEC Gene
RefSeq (mRNA)NM_000445NM_001163540
RefSeq (protein)NP_000436NP_001157012
Location (UCSC)Chr 8:
144.99 – 145.05 Mb
Chr 15:
76.17 – 76.23 Mb
PubMed search[1][2]

Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments.[1] In addition plectin links the cytoskeleton to junctions found in the plasma membrane that structurally connect different cells. By holding these different networks together plectin plays an important role in maintaining the mechanical integrity and viscoelastic properties of tissues.[2]


Plectin can exist in cells as several alternatively-spliced isoforms, all around 500 kDa and >4000 amino acids.[3][4] The structure of plectin is thought to be a dimer consisting of a central coiled coil of alpha helices connecting two large globular domains (one at each terminus). These globular domains are responsible for connecting plectin to its various cytoskeletal targets. The carboxy-terminal domain is made of 6 highly homologous repeating regions. The subdomain between regions five and six of this domain is known to connect to the intermediate filaments cytokeratin and vimentin. At the opposite end of the protein, in the N-terminal domain, a region has been defined as responsible for binding to actin.[5] In 2004, the exact crystal structure of this actin-binding domain (ABD) was determined in mice and shown to be composed of two calponin homology (CH) domains.[6] Plectin is expressed in nearly all mammalian tissues. In cardiac muscle and skeletal muscle, plectin is localized to specialized entities known as Z-discs.[7] Plectin binds several proteins, including vinculin, DES,[8] actin.,[2][9] fodrin,[2][9] microtubule-associating proteins,[2][9] nuclear laminin B.,[2][9] SPTAN1,[10][11] vimentin[10][11][12] and ITGB4.[2][9]


Studies employing a plectin knockout mouse have shed light on the functions of plectin. Pups died 2–3 days after birth, and these mice exhibited marked skin abnormalities, including degeneration of keratinocytes. Skeletal and cardiac muscle tissues were also significantly affected. Cardiac intercalated discs were disintegrated and sarcomeres were irregularly shapen, and intracellular accumulation of aberrant isolated myofibrillar bundles and Z-disc components was also observed. Expression of vinculin in muscle cells was strikingly down-regulated.[13] Through the use of gold-immunoelectron microscopy, immunoblotting and immunofluorescence experiments plectin has been found to associate with all three major components of the cytoskeleton. In muscle, plectin binds to the periphery of Z-discs,[8] and along with the intermediate filament protein desmin, may form lateral linkages among neighboring Z-discs. This interaction between plectin and desmin intermediate filaments also appears to faclitate the close association of myofibrils and mitochondria, both at Z-discs and along the remainder the sarcomere.[14] Plectin also functions to link cytoskeleton to intercellular junctions, such as desmosomes and hemidesmosomes, which link intermediate filament networks between cells. Plectin has been revealed to localize to the desmosomes and in vitro studies have shown that it can form bridges between the desmosome protein, desmoplakin and intermediate filaments.[15] In hemidesmosomes plectin has been shown to interact with the integrin β4 subunits of the hemidesmosome plaque and function in a clamp like manner to crosslink the intermediate filament, cytokeratin to the junction.[16]

Clinical Significance

Mutations in PLEC have been associated with epidermolysis bullosa simplex with muscular dystrophy. Isolated left ventricular non-compaction accompanying epidermolysis bullosa simplex with muscular dystrophy was also noted.[17] Plectin has been proposed as a biomarker for pancreatic cancer.[18][19] Although normally a cytoplasmic protein, plectin is expressed on the cell membrane in pancreatic ductal adenocarcinoma (PDAC) and can therefore be used to target PDAC cells.[18]

See also


  1. ^ Svitkina TM, Verkhovsky AB, Borisy GG (Nov 1996). "Plectin sidearms mediate interaction of intermediate filaments with microtubules and other components of the cytoskeleton". The Journal of Cell Biology 135 (4): 991–1007. PMC 2133373. PMID 8922382. doi:10.1083/jcb.135.4.991. 
  2. ^ a b c d e f Wiche G (Sep 1998). "Role of plectin in cytoskeleton organization and dynamics" (ABSTRACT). Journal of Cell Science. 111 ( Pt 17) (17): 2477–86. PMID 9701547. 
  3. ^  Missing or empty |title= (help)
  4. ^ Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. PMC 4076475. PMID 23965338. doi:10.1161/CIRCRESAHA.113.301151.  edit
  5. ^ Winter L, Wiche G (Jan 2013). "The many faces of plectin and plectinopathies: pathology and mechanisms". Acta Neuropathologica 125 (1). PMID 22864774. doi:10.1007/s00401-012-1026-0. 
  6. ^ Sevcík J, Urbániková L, Kost'an J, Janda L, Wiche G (May 2004). "Actin-binding domain of mouse plectin. Crystal structure and binding to vimentin". European Journal of Biochemistry / FEBS 271 (10): 1873–84. PMID 15128297. doi:10.1111/j.1432-1033.2004.04095.x. 
  7. ^ Zernig G, Wiche G (Jul 1985). "Morphological integrity of single adult cardiac myocytes isolated by collagenase treatment: immunolocalization of tubulin, microtubule-associated proteins 1 and 2, plectin, vimentin, and vinculin". European Journal of Cell Biology 38 (1). PMID 2992982. 
  8. ^ a b Hijikata T, Murakami T, Imamura M, Fujimaki N, Ishikawa H (Mar 1999). "Plectin is a linker of intermediate filaments to Z-discs in skeletal muscle fibers". Journal of Cell Science. 112 ( Pt 6). PMID 10036236. 
  9. ^ a b c d e Steinböck FA, Wiche G (Feb 1999). "Plectin: a cytolinker by design". Biological Chemistry 380 (2). PMID 10195422. doi:10.1515/BC.1999.023. 
  10. ^ a b Herrmann H, Wiche G (Jan 1987). "Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 and to the 240-kilodalton subunit of spectrin". The Journal of Biological Chemistry 262 (3): 1320–5. PMID 3027087. 
  11. ^ a b Brown MJ, Hallam JA, Liu Y, Yamada KM, Shaw S (Jul 2001). "Cutting edge: integration of human T lymphocyte cytoskeleton by the cytolinker plectin". Journal of Immunology 167 (2): 641–5. PMID 11441066. doi:10.4049/jimmunol.167.2.641. 
  12. ^ Favre B, Schneider Y, Lingasamy P, Bouameur JE, Begré N, Gontier Y et al. (May 2011). "Plectin interacts with the rod domain of type III intermediate filament proteins desmin and vimentin". European Journal of Cell Biology 90 (5). PMID 21296452. doi:10.1016/j.ejcb.2010.11.013. 
  13. ^ Andrä K, Lassmann H, Bittner R, Shorny S, Fässler R, Propst F et al. (Dec 1997). "Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture". Genes & Development 11 (23). PMID 9389647. 
  14. ^ Reipert S, Steinböck F, Fischer I, Bittner RE, Zeöld A, Wiche G (Nov 1999). "Association of mitochondria with plectin and desmin intermediate filaments in striated muscle". Experimental Cell Research 252 (2). PMID 10527638. doi:10.1006/excr.1999.4626. 
  15. ^ Huber O (Sep 2003). "Structure and function of desmosomal proteins and their role in development and disease". Cellular and Molecular Life Sciences 60 (9). PMID 14523549. doi:10.1007/s00018-003-3050-7. 
  16. ^ Sonnenberg A, Liem RK (Jun 2007). "Plakins in development and disease". Experimental Cell Research 313 (10). PMID 17499243. doi:10.1016/j.yexcr.2007.03.039. 
  17. ^ Villa CR, Ryan TD, Collins JJ, Taylor MD, Lucky AW, Jefferies JL (Feb 2015). "Left ventricular non-compaction cardiomyopathy associated with epidermolysis bullosa simplex with muscular dystrophy and PLEC1 mutation". Neuromuscular Disorders 25 (2). PMID 25454730. doi:10.1016/j.nmd.2014.09.011. 
  18. ^ a b Kelly KA, Bardeesy N, Anbazhagan R, Gurumurthy S, Berger J, Alencar H et al. (Apr 2008). "Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma". PLoS Medicine 5 (4): e85. PMC 2292750. PMID 18416599. doi:10.1371/journal.pmed.0050085. 
  19. ^ Bausch D, Thomas S, Mino-Kenudson M, Fernández-del CC, Bauer TW, Williams M et al. (Jan 2011). "Plectin-1 as a novel biomarker for pancreatic cancer". Clinical Cancer Research 17 (2): 302–9. PMC 3044444. PMID 21098698. doi:10.1158/1078-0432.CCR-10-0999. 

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