Structure and function of desmosomal transmembrane core and plaque molecules

Kowalczyk, Andrew P.; Stappenbeck, Thaddeus S.; Palka, Helena L.; Virata, M. L.A.; Bornslaeger, Elayne A.; Nilles, Laura A.; Green, Kathleen J.

doi:10.1016/0301-4622(94)85023-2

Cited by 51 publications

(36 citation statements)

References 72 publications

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“…This additional structural interaction of plakoglobin may further reduce the free plakoglobin pool. Indeed, the rate of plakoglobin degradation in transfected cells decreased 15 ± 20-fold when plakoglobin is co-transfected with its desmosomal partners, desmoglein or desmocollin (Kowalczyk et al, 1994). It is noteworthy that both MDCK and 293T cells, that were used in the present and previous studies , are epithelial and contain desmosomes.…”

Section: Discussionmentioning

confidence: 50%

Differential interaction of plakoglobin and β-catenin with the ubiquitin-proteasome system

et al. 2000

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b-Catenin and plakoglobin are closely related armadillo family proteins with shared and distinct properties; Both are associated with cadherins in actin-containing adherens junctions. Plakoglobin is also found in desmosomes where it anchors intermediate ®laments to the desmosomal plaques. b-Catenin, on the other hand, is a component of the Wnt signaling pathway, which is involved in embryonic morphogenesis and tumorigenesis. A key step in the regulation of this pathway involves modulation of b-catenin stability. A multiprotein complex, regulated by Wnt, directs the phosphorylation of bcatenin and its degradation by the ubiquitin-proteasome system. Plakoglobin can also associate with members of this complex, but inhibition of proteasomal degradation has little e ect on its levels while dramatically increasing the levels of b-catenin. b-TrCP, an F-box protein of the SCF E3 ubiquitin ligase complex, was recently shown to play a role in the turnover of b-catenin. To elucidate the basis for the apparent di erences in the turnover of bcatenin and plakoglobin we compared the handling of these two proteins by the ubiquitin-proteasome system. We show here that a deletion mutant of b-TrCP, lacking the F-box, can stabilize the endogenous b-catenin leading to its nuclear translocation and induction of b-catenin/ LEF-1-directed transcription, without a ecting the levels of plakoglobin. However, when plakoglobin was overexpressed, it readily associated with b-TrCP, e ciently competed with b-catenin for binding to b-TrCP and became polyubiquitinated. Fractionation studies revealed that about 85% of plakoglobin in 293 cells, is Triton X-100-insoluble compared to 50% of b-catenin. These results suggest that while both plakoglobin and b-catenin can comparably interact with b-TrCP and the ubiquitination system, the sequestration of plakoglobin by the membrane-cytoskeleton system renders it inaccessible to the proteolytic machinery and stabilizes it.

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Section: Discussionmentioning

confidence: 50%

Differential interaction of plakoglobin and β-catenin with the ubiquitin-proteasome system

et al. 2000

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“…They consist of seven major proteins and glycoproteins. The principal desmosomal proteins are desmoplakins I and H (DpI and II), pakoglobin and B6P or plakophilin; the major glycoproteins are desmoglein (Dsg) and desmocollin 'a' and 'b' (Garrod, 1993;Schmidt et at., 1994;Kowalczyk et al, 1994;Collins and Garrod, 1994, and articles therein). Both desmoglein and desmocollins occur as three distinct isoforms, the products of different genes, which form separate subfamilies of the cadherin family of calcium-dependent adhesion molecules (Buxton et al, 1993;Legan et al, 1994;Schifer et al, 1994;Nuber et al, 1995;Yue et al, 1995).…”

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confidence: 99%

“…The desmoplakins are members of a small family of intermediate filament-associated proteins that includes the 230 kDa bullous pemphigoid antigen and plectin (Garrod, 1993;Kowalczyk et al, 1994). DpI exists as a dimer with a flexible coiled-coil central rod domain and more globular end domains (O'Keefe et al, 1989;Kowalczyk et al, 1994).…”

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confidence: 99%

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Immunohistochemical staining of desmosomal components in oral squamous cell carcinomas and its association with tumour behaviour

Hiraki

Shinohara²,

Ikebe³

et al. 1996

Br J Cancer

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Sumary Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinomas and that may play a role in suppression of invasion and metastasis. We have shown previously that immunohistochemical staining for the major desmosomal glycoprotein, desmoglein (Dsg), is reduced in some cases of squamous cell carcinoma (SCC) of the head and neck, and that reduced staining correlates with lymph node involvement. Desmosomes are multicomponent organelles. We therefore sought to determine whether another major desmosomal mokcule, desmoplakin (Dp), showed similar reduced expression to that shown by desmoglein. We have stained 65 specimens of primary SCC of the oral cavity (37 non-metastatic and 28 metatastic) with monoclonal antibodies to both desmoglein and desmoplak-in. We show that reduction of Dp staining correlates with loss of differentiation of the primary tumour, degree of invasion and presence of lymph node metastases. Similar correlations were found with Dsg staining. There was also correlation between reduction in Dp staining and reduction in Dsg staining. It is concluded that down-regulation of desmosomal expression occurs in some cases of SCC of the oral cavity and is associated with invasion and metastasis. Desmosomes may have an invasion and metastasis suppressor function.

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“…2D; Franke et al, 1982). Through its coiled-coil region, desmoplakin has been suggested to form homodimers (Kowalczyk et al, 1994), while its NH 2 -terminal region binds to plakoglobins and plakophilins, targeting them to desmosomes (Bornslaeger et al, 1996;Bornslaeger et al, 2001;Holthofer et al, 2007;Kowalczyk et al, 1999). Its COOHterminal tail is composed of three plakin-repeat domains and a Gly-Ser-Arg rich motif; both shown to mediate binding to desmin (Choi et al, 2002;Getsios et al, 2004).…”

Section: Plakinsmentioning

confidence: 99%