Plectin

Last updated
PLEC
Protein PLEC1 PDB 1mb8.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PLEC , EBS1, EBSMD, EBSND, EBSO, EBSOG, EBSPA, HD1, LGMD2Q, PCN, PLEC1, PLEC1b, PLTN, plectin, LGMDR17, EBS5D, EBS5C, EBS5B, EBS5A
External IDs OMIM: 601282 MGI: 1277961 HomoloGene: 384 GeneCards: PLEC
Orthologs
SpeciesHumanMouse
Entrez

5339

18810

Ensembl

ENSG00000178209

ENSMUSG00000022565

UniProt

Q15149

Q9QXS1

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC) Chr 8: 143.92 – 143.98 Mb Chr 15: 76.06 – 76.12 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] 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. [6]

Structure

Plectin can exist in cells as several alternatively-spliced isoforms, all around 500 kDa and >4000 amino acids. [7] [8] 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. [9] 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. [10] Plectin is expressed in nearly all mammalian tissues. In cardiac muscle and skeletal muscle, plectin is localized to specialized entities known as Z-discs. [11] Plectin binds several proteins, including vinculin, DES, [12] actin, [6] [13] fodrin, [6] [13] microtubule-associating proteins, [6] [13] nuclear laminin B, [6] [13] SPTAN1, [14] [15] vimentin [14] [15] [16] and ITGB4. [6] [13]

Function

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. [17] 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, [12] 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 facilitate the close association of myofibrils and mitochondria, both at Z-discs and along the remainder the sarcomere. [18] 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. [19] 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 link the intermediate filament cytokeratin to the junction. [20]

Clinical significance

Mutations in PLEC have been associated with epidermolysis bullosa simplex with muscular dystrophy. [21] A missense variant of PLEC has been recently proposed as a cause of atrial fibrillation in some populations. [22] Isolated left ventricular non-compaction accompanying epidermolysis bullosa simplex with muscular dystrophy was also noted. [23] Plectin has been proposed as a biomarker for pancreatic cancer. [24] [25] 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. [24]

See also

Related Research Articles

<span class="mw-page-title-main">Cytoskeleton</span> Network of filamentous proteins that forms the internal framework of cells

The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components: microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth or disassembly depending on the cell's requirements.

<span class="mw-page-title-main">Intermediate filament</span> Cytoskeletal structure

Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate Branchiostoma.

<span class="mw-page-title-main">Desmosome</span> Cell junction involved in cell-to-cell adhesion

A desmosome, also known as a macula adherens, is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides of plasma membranes. Desmosomes are one of the stronger cell-to-cell adhesion types and are found in tissue that experience intense mechanical stress, such as cardiac muscle tissue, bladder tissue, gastrointestinal mucosa, and epithelia.

Type II keratins constitutes the Type II intermediate filaments (IFs) of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells. The type 2 cytokeratins consist of basic or neutral, high molecular weight proteins which in vivo are arranged in pairs of heterotypic Type I and Type II keratin chains, coexpressed during differentiation of simple and stratified epithelial tissues. It has been seen that Type II Keratins are developed before Type 1 keratins during human embryonic development.

<span class="mw-page-title-main">Keratin 14</span> Protein-coding gene in the species Homo sapiens

Keratin 14 is a member of the type I keratin family of intermediate filament proteins. Keratin 14 was the first type I keratin sequence determined. Keratin 14 is also known as cytokeratin-14 (CK-14) or keratin-14 (KRT14). In humans it is encoded by the KRT14 gene.

<span class="mw-page-title-main">Hemidesmosome</span>

Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to focal adhesions, as they both attach cells to the extracellular matrix. Instead of desmogleins and desmocollins in the extracellular space, hemidesmosomes utilize integrins. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the lamina lucida, which is part of the basal lamina. Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or carcinoma cell intrusion.

<span class="mw-page-title-main">Vimentin</span> Type III intermediate filament protein

Vimentin is a structural protein that in humans is encoded by the VIM gene. Its name comes from the Latin vimentum which refers to an array of flexible rods.

<span class="mw-page-title-main">Tropomyosin</span> Protein

Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in many animal and fungal cells. In animals, it is an important component of the muscular system which works in conjunction with troponin to regulate muscle contraction. It is present in smooth and striated muscle tissues, which can be found in various organs and body systems, including the heart, blood vessels, respiratory system, and digestive system. In fungi, tropomyosin is found in cell walls and helps maintain the structural integrity of cells.

<span class="mw-page-title-main">Protein filament</span> Long chain of protein monomers

In biology, a protein filament is a long chain of protein monomers, such as those found in hair, muscle, or in flagella. Protein filaments form together to make the cytoskeleton of the cell. They are often bundled together to provide support, strength, and rigidity to the cell. When the filaments are packed up together, they are able to form three different cellular parts. The three major classes of protein filaments that make up the cytoskeleton include: actin filaments, microtubules and intermediate filaments.

<span class="mw-page-title-main">Desmoplakin</span> Protein found in humans

Desmoplakin is a protein in humans that is encoded by the DSP gene. Desmoplakin is a critical component of desmosome structures in cardiac muscle and epidermal cells, which function to maintain the structural integrity at adjacent cell contacts. In cardiac muscle, desmoplakin is localized to intercalated discs which mechanically couple cardiac cells to function in a coordinated syncytial structure. Mutations in desmoplakin have been shown to play a role in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, where it may present with acute myocardial injury; striate palmoplantar keratoderma, Carvajal syndrome and paraneoplastic pemphigus.

<span class="mw-page-title-main">Keratin 5</span>

Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the KRT5 gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.

<span class="mw-page-title-main">Collagen, type XVII, alpha 1</span> Mammalian protein found in humans

Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and colleagues in 1990.

<span class="mw-page-title-main">Epidermolysis bullosa dystrophica</span> Medical condition

Epidermolysis bullosa dystrophica or dystrophic EB (DEB) is an inherited disease affecting the skin and other organs.

<span class="mw-page-title-main">Actin, cytoplasmic 2</span> Protein-coding gene in the species Homo sapiens

Actin, cytoplasmic 2, or gamma-actin is a protein that in humans is encoded by the ACTG1 gene. Gamma-actin is widely expressed in cellular cytoskeletons of many tissues; in adult striated muscle cells, gamma-actin is localized to Z-discs and costamere structures, which are responsible for force transduction and transmission in muscle cells. Mutations in ACTG1 have been associated with nonsyndromic hearing loss and Baraitser-Winter syndrome, as well as susceptibility of adolescent patients to vincristine toxicity.

<span class="mw-page-title-main">Collagen, type VII, alpha 1</span> Protein found in humans

Collagen alpha-1(VII) chain is a protein that in humans is encoded by the COL7A1 gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epidermal junction in the basement membrane. Mutations in COL7A1 cause all types of dystrophic epidermolysis bullosa, and the exact mutations vary based on the specific type or subtype. It has been shown that interactions between the NC-1 domain of collagen VII and several other proteins, including laminin-5 and collagen IV, contribute greatly to the overall stability of the basement membrane.

<span class="mw-page-title-main">Integrin beta 4</span> Protein-coding gene in the species Homo sapiens

Integrin, beta 4 (ITGB4) also known as CD104, is a human gene.

<span class="mw-page-title-main">SPTAN1</span> Protein-coding gene in the species Homo sapiens

Alpha II-spectrin, also known as Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene. Alpha II-spectrin is expressed in a variety of tissues, and is highly expressed in cardiac muscle at Z-disc structures, costameres and at the sarcolemma membrane. Mutations in alpha II-spectrin have been associated with early infantile epileptic encephalopathy-5, and alpha II-spectrin may be a valuable biomarker for Guillain–Barré syndrome and infantile congenital heart disease.

<span class="mw-page-title-main">FLNC (gene)</span> Protein-coding gene in the species Homo sapiens

Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a protein that in humans is encoded by the FLNC gene. Filamin-C is mainly expressed in cardiac and skeletal muscles, and functions at Z-discs and in subsarcolemmal regions.

<span class="mw-page-title-main">MYOT</span> Mammalian protein found in Homo sapiens

Myotilin is a protein that in humans is encoded by the MYOT gene. Myotilin also known as TTID is a muscle protein that is found within the Z-disc of sarcomeres.

<span class="mw-page-title-main">Irwin McLean</span> Emeritus Professor of Genetic Medicine

(William Henry) Irwin McLean FRS FRSE FMedSci is Emeritus Professor of Genetic Medicine, at the School of Life Sciences, University of Dundee.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000178209 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022565 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ 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. doi:10.1083/jcb.135.4.991. PMC   2133373 . PMID   8922382.
  6. 1 2 3 4 5 6 Wiche G (Sep 1998). "Role of plectin in cytoskeleton organization and dynamics" (abstract). Journal of Cell Science. 111 (17): 2477–86. doi:10.1242/jcs.111.17.2477. PMID   9701547.
  7. ↑ "Plectin in: Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)". Archived from the original on 2016-03-05. Retrieved 2015-04-13.
  8. ↑ 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 (2013-10-12). "Integration of Cardiac Proteome Biology and Medicine by a Specialized Knowledgebase". Circulation Research. 113 (9): 1043–1053. doi:10.1161/CIRCRESAHA.113.301151. ISSN   0009-7330. PMC   4076475 . PMID   23965338.
  9. ↑ Winter L, Wiche G (Jan 2013). "The many faces of plectin and plectinopathies: pathology and mechanisms". Acta Neuropathologica. 125 (1): 77–93. doi:10.1007/s00401-012-1026-0. PMID   22864774. S2CID   12429741.
  10. ↑ 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. 271 (10): 1873–84. doi: 10.1111/j.1432-1033.2004.04095.x . PMID   15128297.
  11. ↑ 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): 113–22. PMID   2992982.
  12. 1 2 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 (6): 867–76. doi:10.1242/jcs.112.6.867. PMID   10036236.
  13. 1 2 3 4 5 Steinböck FA, Wiche G (Feb 1999). "Plectin: a cytolinker by design". Biological Chemistry. 380 (2): 151–8. doi: 10.1515/BC.1999.023 . PMID   10195422. S2CID   46726381.
  14. 1 2 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. doi: 10.1016/S0021-9258(19)75789-5 . PMID   3027087.
  15. 1 2 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. doi: 10.4049/jimmunol.167.2.641 . PMID   11441066.
  16. ↑ Favre B, Schneider Y, Lingasamy P, Bouameur JE, Begré N, Gontier Y, Steiner-Champliaud MF, Frias MA, Borradori L, Fontao L (May 2011). "Plectin interacts with the rod domain of type III intermediate filament proteins desmin and vimentin". European Journal of Cell Biology. 90 (5): 390–400. doi:10.1016/j.ejcb.2010.11.013. PMID   21296452.
  17. ↑ Andrä K, Lassmann H, Bittner R, Shorny S, Fässler R, Propst F, Wiche G (Dec 1997). "Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture". Genes & Development. 11 (23): 3143–56. doi:10.1101/gad.11.23.3143. PMC   316746 . PMID   9389647.
  18. ↑ 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): 479–91. doi:10.1006/excr.1999.4626. PMID   10527638.
  19. ↑ Huber O (Sep 2003). "Structure and function of desmosomal proteins and their role in development and disease". Cellular and Molecular Life Sciences. 60 (9): 1872–90. doi:10.1007/s00018-003-3050-7. PMID   14523549. S2CID   11557417.
  20. ↑ Sonnenberg A, Liem RK (Jun 2007). "Plakins in development and disease". Experimental Cell Research. 313 (10): 2189–203. doi:10.1016/j.yexcr.2007.03.039. PMID   17499243.
  21. ↑ Bardhan A, Bruckner-Tuderman L, Chapple IL, Fine JD, Harper N, Has C, Magin TM, Marinkovich MP, Marshall JF, McGrath JA, Mellerio JE (2020-09-24). "Epidermolysis bullosa". Nature Reviews Disease Primers. 6 (1): 78. doi:10.1038/s41572-020-0210-0. ISSN   2056-676X. PMID   32973163. S2CID   221861310.
  22. ↑ Thorolfsdottir RB, Sveinbjornsson G, Sulem P, Helgadottir A, Gretarsdottir S, Benonisdottir S, Magnusdottir A, Davidsson OB, Rajamani S, Roden DM, Darbar D, Pedersen TR, Sabatine MS, Jonsdottir I, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K (2017). "A Missense Variant in PLEC Increases Risk of Atrial Fibrillation". Journal of the American College of Cardiology. 70 (17): 2157–2168. doi:10.1016/j.jacc.2017.09.005. PMC   5704994 . PMID   29050564.
  23. ↑ 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): 165–8. doi:10.1016/j.nmd.2014.09.011. PMID   25454730. S2CID   25193440.
  24. 1 2 Kelly KA, Bardeesy N, Anbazhagan R, Gurumurthy S, Berger J, Alencar H, Depinho RA, Mahmood U, Weissleder R (Apr 2008). "Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma". PLOS Medicine. 5 (4): e85. doi: 10.1371/journal.pmed.0050085 . PMC   2292750 . PMID   18416599.
  25. ↑ Bausch D, Thomas S, Mino-Kenudson M, Fernández-del CC, Bauer TW, Williams M, Warshaw AL, Thayer SP, Kelly KA (Jan 2011). "Plectin-1 as a novel biomarker for pancreatic cancer". Clinical Cancer Research. 17 (2): 302–9. doi:10.1158/1078-0432.CCR-10-0999. PMC   3044444 . PMID   21098698.

Further reading

  1. ↑ 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 (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–1053. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.