Plectin

Plectin is a giant protein (c500 kDa) 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.cite journal | author = Svitkina TM, Verkhovsky AB, Borisy GG | title = Plectin sidearms mediate interaction of intermediate filaments with microtubules and other components of the cytoskeleton | journal = J. Cell Biol. | volume = 135 | issue = 4 | pages = 991–1007 | year = 1996 | pmid = 8922382 | doi = 10.1083/jcb.135.4.991 | issn = ] 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.cite journal | author = Wiche G | title = Role of plectin in cytoskeleton organization and dynamics | journal = J. Cell. Sci. | volume = 111 ( Pt 17) | issue = | pages = 2477–86 | year = 1998 | pmid = 9701547 | doi = | issn = | url = http://jcs.biologists.org/cgi/content/abstract/111/17/2477 | format = abstract ]

Structure

The structure of plectin is thought to be a dimer consisting of a central coiled coil of alpha helices connected to large globular domains 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. 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.cite journal | author = Sevcík J, Urbániková L, Kost'an J, Janda L, Wiche G | title = Actin-binding domain of mouse plectin. Crystal structure and binding to vimentin | journal = Eur. J. Biochem. | volume = 271 | issue = 10 | pages = 1873–84 | year = 2004 | pmid = 15128297 | doi = 10.1111/j.1432-1033.2004.04095.x | issn = ]

Function

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. With the use of microscopy especially plectin has been shown to directly connect microtubules to intermediate filaments as well as to each other. While plectin has been observed to mediate interactions between actin and intermediate filaments and associate with each independently, a direct linkage by plectin between these two filaments has not been completely proven. It may be that plectin actually connects to proteins associated with each rather than directly. Besides serving as a linker protein between the main elements of the cytoskeleton, plectin also forms connections between other cytoskeletally related proteins as well. Plectin has been shown to directly link Myosin II motor proteins and intermediate filaments. In in vitro assays plectin has been found to bind subplasma membrane skeleton proteins such as alpha-spectrin and fodrin.Over the past decade plectin has been identified as an important component linking the cytoskeleton to intercellular junctions which enable the structural integrity of a tissue as a whole. Two such junctions, Desmosomes and Hemidesmosomes which link intermediate filament networks between cells have been shown to associate with plectin. 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. 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.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Pfendner E, Rouan F, Uitto J |title=Progress in epidermolysis bullosa: the phenotypic spectrum of plectin mutations. |journal=Exp. Dermatol. |volume=14 |issue= 4 |pages= 241–9 |year= 2005 |pmid= 15810881 |doi= 10.1111/j.0906-6705.2005.00324.x
*cite journal | author=Foisner R, Traub P, Wiche G |title=Protein kinase A- and protein kinase C-regulated interaction of plectin with lamin B and vimentin. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 9 |pages= 3812–6 |year= 1991 |pmid= 2023931 |doi=
*cite journal | author=Herrmann H, Wiche G |title=Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 and to the 240-kilodalton subunit of spectrin. |journal=J. Biol. Chem. |volume=262 |issue= 3 |pages= 1320–5 |year= 1987 |pmid= 3027087 |doi=
*cite journal | author=Malecz N, Foisner R, Stadler C, Wiche G |title=Identification of plectin as a substrate of p34cdc2 kinase and mapping of a single phosphorylation site. |journal=J. Biol. Chem. |volume=271 |issue= 14 |pages= 8203–8 |year= 1996 |pmid= 8626512 |doi=
*cite journal | author=Liu CG, Maercker C, Castañon MJ, "et al." |title=Human plectin: organization of the gene, sequence analysis, and chromosome localization (8q24). |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 9 |pages= 4278–83 |year= 1996 |pmid= 8633055 |doi=
*cite journal | author=Gache Y, Chavanas S, Lacour JP, "et al." |title=Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy. |journal=J. Clin. Invest. |volume=97 |issue= 10 |pages= 2289–98 |year= 1996 |pmid= 8636409 |doi=
*cite journal | author=Smith FJ, Eady RA, Leigh IM, "et al." |title=Plectin deficiency results in muscular dystrophy with epidermolysis bullosa. |journal=Nat. Genet. |volume=13 |issue= 4 |pages= 450–7 |year= 1996 |pmid= 8696340 |doi= 10.1038/ng0896-450
*cite journal | author=McLean WH, Pulkkinen L, Smith FJ, "et al." |title=Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. |journal=Genes Dev. |volume=10 |issue= 14 |pages= 1724–35 |year= 1996 |pmid= 8698233 |doi=
*cite journal | author=Nikolic B, Mac Nulty E, Mir B, Wiche G |title=Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions. |journal=J. Cell Biol. |volume=134 |issue= 6 |pages= 1455–67 |year= 1996 |pmid= 8830774 |doi=
*cite journal | author=Pulkkinen L, Smith FJ, Shimizu H, "et al." |title=Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. |journal=Hum. Mol. Genet. |volume=5 |issue= 10 |pages= 1539–46 |year= 1997 |pmid= 8894687 |doi=
*cite journal | author=Gress TM, Müller-Pillasch F, Geng M, "et al." |title=A pancreatic cancer-specific expression profile. |journal=Oncogene |volume=13 |issue= 8 |pages= 1819–30 |year= 1996 |pmid= 8895530 |doi=
*cite journal | author=Andrä K, Nikolic B, Stöcher M, "et al." |title=Not just scaffolding: plectin regulates actin dynamics in cultured cells. |journal=Genes Dev. |volume=12 |issue= 21 |pages= 3442–51 |year= 1998 |pmid= 9808630 |doi=
*cite journal | author=Banwell BL, Russel J, Fukudome T, "et al." |title=Myopathy, myasthenic syndrome, and epidermolysis bullosa simplex due to plectin deficiency. |journal=J. Neuropathol. Exp. Neurol. |volume=58 |issue= 8 |pages= 832–46 |year= 1999 |pmid= 10446808 |doi=
*cite journal | author=Geerts D, Fontao L, Nievers MG, "et al." |title=Binding of integrin alpha6beta4 to plectin prevents plectin association with F-actin but does not interfere with intermediate filament binding. |journal=J. Cell Biol. |volume=147 |issue= 2 |pages= 417–34 |year= 1999 |pmid= 10525545 |doi=
*cite journal | author=Stegh AH, Herrmann H, Lampel S, "et al." |title=Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosis. |journal=Mol. Cell. Biol. |volume=20 |issue= 15 |pages= 5665–79 |year= 2000 |pmid= 10891503 |doi=
*cite journal | author=Bauer JW, Rouan F, Kofler B, "et al." |title=A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency. |journal=Am. J. Pathol. |volume=158 |issue= 2 |pages= 617–25 |year= 2001 |pmid= 11159198 |doi=
*cite journal | author=Henzler T, Harmache A, Herrmann H, "et al." |title=Fully functional, naturally occurring and C-terminally truncated variant human immunodeficiency virus (HIV) Vif does not bind to HIV Gag but influences intermediate filament structure. |journal=J. Gen. Virol. |volume=82 |issue= Pt 3 |pages= 561–73 |year= 2001 |pmid= 11172097 |doi=
*cite journal | author=Nakano A, Pulkkinen L, Murrell D, "et al." |title=Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations. |journal=Pediatr. Res. |volume=49 |issue= 5 |pages= 618–26 |year= 2001 |pmid= 11328943 |doi=
*cite journal | author=Brown MJ, Hallam JA, Liu Y, "et al." |title=Cutting edge: integration of human T lymphocyte cytoskeleton by the cytolinker plectin. |journal=J. Immunol. |volume=167 |issue= 2 |pages= 641–5 |year= 2001 |pmid= 11441066 |doi=
*cite journal | author=Koss-Harnes D, Høyheim B, Anton-Lamprecht I, "et al." |title=A site-specific plectin mutation causes dominant epidermolysis bullosa simplex Ogna: two identical de novo mutations. |journal=J. Invest. Dermatol. |volume=118 |issue= 1 |pages= 87–93 |year= 2002 |pmid= 11851880 |doi= 10.1046/j.0022-202x.2001.01591.x

External links

*
*

PBB_Controls
update_page = yes
require_manual_inspection = no
update_protein_box = yes
update_summary = no
update_citations = yes