Structure of Desmoplakin and Its Association with Intermediate Filaments

Green, Kathleen J.; Stappenbeck, Thaddeus S; Parry, David; Virata, M. L.A.

doi:10.1111/j.1346-8138.1992.tb03777.x

Cited by 39 publications

(26 citation statements)

References 17 publications

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“…as type A, B, and C (20). Desmoplakin has three such domains, one of type A, one of type B, and one of type C, whereas of the six plectin R domains, five are type B (R1-5), and one is type C (R6) (21).…”

Section: Methodsmentioning

confidence: 99%

Oxidation and Nitrosylation of Cysteines Proximal to the Intermediate Filament (IF)-binding Site of Plectin

Spurný¹,

Abdoulrahman²,

Janda³

et al. 2007

Journal of Biological Chemistry

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As an intermediate filament (IF)-based cytolinker protein, plectin plays a key role in the maintenance of cellular cytoarchitecture and serves at the same time as a scaffolding platform for signaling cascades. Consisting of six structural repeats (R1-6) and harboring binding sites for different IF proteins and proteins involved in signaling, the plectin C-terminal domain is of strategic functional importance. Depending on the species, it contains at least 13 cysteines, 4 of which reside in the R5 domain. To investigate the structural and biological functions of R5 cysteines, we used cysteine-to-serine mutagenesis and spectroscopic, biochemical, and functional analyses. Urea-induced unfolding experiments indicated that wild-type R5 in the oxidized, disulfide bond-mediated conformation was more stable than its cysteine-free mutant derivative. The binding affinity of R5 for vimentin was significantly higher, however, when the protein was in the reduced, more relaxed conformation. Of the four R5 cysteines, one (Cys4) was particularly reactive as reflected by its ability to form disulfide bridges with R5 Cys1 and to serve as a target for nitrosylation in vitro. Using immortalized endothelial cell cultures from mice, we show that endogenous plectin is nitrosylated in vivo, and we found that NO donorinduced IF collapse proceeds dramatically faster in plectin-deficient compared with wild-type cells. Our data suggest an antagonistic role of plectin in nitrosylation (oxidative stress)-mediated alterations of IF cytoarchitecture and a possible role of R5 Cys4 as a regulatory switch.

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Section: Methodsmentioning

confidence: 99%

Oxidation and Nitrosylation of Cysteines Proximal to the Intermediate Filament (IF)-binding Site of Plectin

Spurný¹,

Abdoulrahman²,

Janda³

et al. 2007

Journal of Biological Chemistry

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“…5) (Choi et al 2002;Getsios et al 2004b;Yin and Green 2004). There are two desmoplakin isoforms (I and II), with desmoplakin II missing approximately two-thirds of the rod domain (Green et al 1992a). …”

Section: Desmoplakinmentioning

confidence: 99%

The Desmosome

Delva¹,

Tucker²,

Kowalczyk³

2009

Cold Spring Harbor Perspectives in Biology

348

310

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“…These proteins serve as cytolinkers and/or scaffolding proteins, connecting IF to other cytoskeletal networks and/or distinct sites at the plasma membrane. Plakins are predicted to form homodimers with a central coiled-coil domain flanked by globular end domains (Green et al, 1992a;Green et al, 1992b;Ruhrberg and Watt, 1997). The N-terminal region of DP encompasses a so-called plakin domain harboring ␣-helical bundles (Green et al, 1990) and mediates its localization to desmosomes by binding to plakoglobin and plakophilins (Stappenbeck and Green, 1992;Stappenbeck et al, 1993;Kouklis et al, 1994;Cowin and Burke, 1996;Kowalczyk et al, 1997;Smith and Fuchs, 1998).…”

Section: Introductionmentioning

confidence: 99%

New insights into the molecular basis of desmoplakinand desmin-related cardiomyopathies

Lapouge

Fontao

Champliaud

et al. 2006

Journal of Cell Science

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Desmosomes are intercellular adhesive complexes that anchor the intermediate filament cytoskeleton to the cell membrane in epithelia and cardiac muscle cells. The desmosomal component desmoplakin plays a key role in tethering various intermediate filament networks through its C-terminal plakin repeat domain. To gain better insight into the cytoskeletal organization of cardiomyocytes, we investigated the association of desmoplakin with desmin by cell transfection, yeast two-hybrid, and/or in vitro binding assays. The results indicate that the association of desmoplakin with desmin depends on sequences within the linker region and C-terminal extremity of desmoplakin, where the B and C subdomains contribute to efficient binding; a potentially phosphorylatable serine residue in the C-terminal extremity of desmoplakin affects its association with desmin; the interaction of desmoplakin with non-filamentous desmin requires sequences contained within the desmin C-terminal rod portion and tail domain in yeast, whereas in in vitro binding studies the desmin tail is dispensable for association; and mutations in either the C-terminus of desmoplakin or the desmin tail linked to inherited cardiomyopathy seem to impair desmoplakindesmin interaction. These studies increase our understanding of desmoplakin-intermediate filament interactions, which are important for maintenance of cytoarchitecture in cardiomyocytes, and give new insights into the molecular basis of desmoplakin- and desmin-related human diseases.

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Structure of Desmoplakin and Its Association with Intermediate Filaments

Cited by 39 publications

References 17 publications

Oxidation and Nitrosylation of Cysteines Proximal to the Intermediate Filament (IF)-binding Site of Plectin

Oxidation and Nitrosylation of Cysteines Proximal to the Intermediate Filament (IF)-binding Site of Plectin

The Desmosome

New insights into the molecular basis of desmoplakinand desmin-related cardiomyopathies

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