Abstract:
:Desmosomes are intercellular junctions specialised for strong adhesion that are prominent in the epidermis and heart muscle. Defective desmosomal function due to inherited mutations in the constitutive desmosomal gene desmoplakin (DSP) causes skin or heart disorders and in some instances both. Different mutations have different disease-causing molecular mechanisms as evidenced by the varying phenotypes resulting from mutations affecting different domains of the same protein, but the majority of these mechanisms remain to be determined. Here, we studied two mutations in DSP that lead to different dosages of the two major DSP splice variants, DSPI and DSPII, and compared their molecular mechanisms. One of the mutations results in total DSP haploinsufficiency and is associated with autosomal dominant striate palmoplantar keratoderma (PPK). The other leads to complete absence of DSPI and the minor isoform DSPIa but normal levels of DSPII, and is associated with autosomal recessive epidermolytic PPK, woolly hair and severe arrhythmogenic dilated cardiomyopathy. Using siRNA treatments to mimic these two mutations and additionally a DSPII-specific siRNA, we found striking differences between DSP isoforms with respect to keratinocyte adhesion upon cellular stress with DSPII being the key component in intermediate filament (IF) stability and desmosome-mediated adhesion. In addition, reduction in DSP expression reduced the amount of plakophilin 1, desmocollin (DSC) 2 and DSC3 with DSPI having a greater influence than DSPII on the expression levels of DSC3. These results suggest that the two major DSP splice variants are not completely redundant in function and that DSPII dosage is particularly important for desmosomal adhesion in the skin.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Cabral RM,Tattersall D,Patel V,McPhail GD,Hatzimasoura E,Abrams DJ,South AP,Kelsell DPdoi
10.1242/jcs.084152subject
Has Abstractpub_date
2012-06-15 00:00:00pages
2853-61issue
Pt 12eissn
0021-9533issn
1477-9137pii
jcs.084152journal_volume
125pub_type
杂志文章abstract::The activated leukocyte cell adhesion molecule (ALCAM) is dynamically regulated by the actin cytoskeleton. In this study we explored the molecular mechanisms and signaling pathways underlying the cytoskeletal restraints of this homotypic adhesion molecule. We observed that ALCAM-mediated adhesion induced by cytoskelet...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01139
更新日期:2004-06-01 00:00:00
abstract::Injection of the circular plasmid FV1 (derived from type I bovine papilloma virus) into Xenopus eggs before the start of the first cell cycle dramatically increases the efficiency of plasmid replication once eggs are chemically activated. We call this the preloading effect and report kinetic and quantitative character...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::The nature, intracellular distribution, and role of proteins synthesized during meiotic maturation of mouse oocytes in vitro have been examined. Proteins synthesized during the initial stages of maturation are concentrated within the nucleus (germinal vesicle) and become intimately associated with the condensing chrom...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract::We have isolated mini-titin from the nematodes Ascaris lumbricoides and Caenorhabditis elegans under native conditions using a modification in the procedure to prepare this protein from insect muscle. The proteins have an apparent molecular weight of 600,000 and appear in oriented specimens as flexible thin rods with ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::Casein kinase 1 (CK1) plays central roles in various signal transduction pathways and performs many cellular activities. For many years CK1 was thought to act independently of modulatory subunits and in a constitutive manner. Recently, DEAD box RNA helicases, in particular DEAD box RNA helicase 3 X-linked (DDX3X), wer...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.207316
更新日期:2018-01-04 00:00:00
abstract::Freeze-fracture of fixed and unfixed tissue, lanthanum tracer and conventional thin-section studies have revealed 2 new types of septate junction in the class Anthozoa, phylum Coelenterata. These new junctions have the 15-18-nm intercellular spacing of all other described septate junctions and are found around the api...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1980-04-01 00:00:00
abstract::The dipeptide glycyl-l-phenylalanine 2-naphthylamide (GPN) is widely used to perturb lysosomes because its cleavage by the lysosomal enzyme cathepsin C is proposed to rupture lysosomal membranes. We show that GPN evokes a sustained increase in lysosomal pH (pHly), and transient increases in cytosolic pH (pHcyt) and Ca...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.223883
更新日期:2019-02-01 00:00:00
abstract::The mechanical implementation of phagocytosis requires a well-coordinated deployment of cytoplasm and membrane during the creation of a phagosome. We follow the time course of this process in initially round passive neutrophils presented with antibody-coated beads of radii 1.1 to 5.5 microm. In particular, we monitor ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02275
更新日期:2005-05-01 00:00:00
abstract::New concepts in cell organization emerged in a medieval castle during a snowy week in January 2017 in the middle of the Austrian Alps. The occasion was the 10th Annaberg EMBO workshop in Goldegg am See; organized by Gabriele Seethaler, Catherine Rabouille and Marino Zerial. There were 95 participants, including many w...
journal_title:Journal of cell science
pub_type:
doi:10.1242/jcs.206219
更新日期:2017-07-15 00:00:00
abstract::Pharmacological inhibitors of JNK (SP600125) and p38 (PD169316) sensitize tumor cells to Fas-mediated apoptosis. PD169316 is less potent than SP600125 and diminishes its effect when present together. Because the p38 isoforms that promote (p38alpha) or inhibit (p38beta) apoptosis are both suppressed by PD169316, we inv...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01573
更新日期:2004-12-15 00:00:00
abstract::We have previously demonstrated that the subcellular distribution of the adhesion plaque protein, talin, changes dramatically in human platelets in response to platelet activation (Beckerle et al., J. Cell Biol. 109, 3333-3346, 1989). Talin is uniformly distributed throughout the cytoplasm of resting platelets. Howeve...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::We have investigated the intracellular distribution of insoluble fibronectin in HeLa tumour cells. By indirect immunofluorescence microscopy fibronectin was detected in the nuclear region, but not in the region of the cell surface. Isolated nuclei and isolated nuclear matrices also stained for fibronectin. By quantita...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::In epithelial cells integrins are segregated on discrete domains of the plasma membrane. Redistribution may also occur during migration or differentiation. However, little is known about the mechanisms that control such redistribution. Receptor internalization may be a part of one such mechanism. We developed a quanti...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::We have previously reported that foetal and adult fibroblasts display distinctive migratory phenotypes when cultured on three-dimensional collagen gels. Both skin and tumour-derived fibroblasts from a significant proportion of patients with breast cancer were subsequently observed to display foetal-like migratory beha...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::Integrin alpha1beta1 is a collagen receptor predominantly found in mesenchymal tissues. Mice lacking this receptor are viable. We have previously suggested that alpha1beta1 might participate in the down-regulation of collagen gene expression observed in cells suspended inside collagen gels. The results presented here ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::Expression of the vitronectin gene was detected in advanced human astrocytoma by in situ hybridization, whereas vitronectin mRNA was undetectable in low grade tumors or in normal adult brain, indicating that vitronectin is a marker of malignant astrocytoma. We established a model of human astrocytoma by transplanting ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::The movement of cells in small groups, or clusters, was studied in vitro using epithelioid cells from Gordon-Kosswig melanomas (from poecelid fish) and time-lapse cinemicrography. Tumour explants cultured on glass yield cell sheets from which groups of cells separate and become independently motile clusters. These clu...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::Monoclonal mouse hybridoma antibodies were obtained for secreted cellular fibronectin (cFn) from A8387 fibrosarcoma cells. One of them, 52-DH1 (DH), reacted exclusively with cFns but not with plasma Fns (pFns) in immunoblotting and solid-phase EIA. The DH antibody also recognized thermolysin cFn fragments and beta-gal...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::Changes in the cytoskeletal structure of cultured A10 smooth muscle cells induced by calyculin-A (CL-A), a potent inhibitor of types 1 and 2A protein phosphatases, were analyzed using indirect fluorescence techniques. In the presence of 1 x 10(-7) M CL-A the cells became round and subsequently detached from the substr...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::In human red blood cells, protein 4.1 (4.1R) stabilizes the spectrin-actin network and anchors it to the plasma membrane. To contribute to the characterization of functional roles of 4.1R in nonerythroid cells, we analysed the effect of ectopic expression of 4.1R isoforms on interphase microtubules in fibroblastic cel...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01544
更新日期:2004-12-01 00:00:00
abstract::Agrin, a 200 kDa extracellular matrix protein, participates in the maturation of the postsynaptic target at the neuromuscular junction. Although agrin has also been detected in central neurons, little is known about its role in the formation of their synapses. In the present study, the pattern of expression, localizat...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::The transbilayer dynamics of lipids in the plasma membrane of mammalian sperm cells is crucial for the fertilization process. Here, the transbilayer movement and distribution of phospholipids in the plasma membrane of fresh, ejaculated and cryopreserved ram spermatozoa was studied by labeling cells with fluorescent an...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::Chick embryo fibroblasts cultivated in vitro and Ehrlich ascites tumor cells (in vivo or in vitro) have been treated with amphotericin B. Cell multiplication is strongly inhibited. Large clear zones appear in the fibroblast nucleoi (phase-contrast and electron-microscope observations). Many treated fibroblasts and tum...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract::Drosophila neural stem cells or neuroblasts undergo typical asymmetric cell division. An evolutionally conserved protein complex, comprising atypical protein kinase C (aPKC), Bazooka (Par-3) and Par-6, organizes cell polarity to direct these asymmetric divisions. Aurora-A (AurA) is a key molecule that links the divisi...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.050955
更新日期:2009-09-15 00:00:00
abstract::SNAREs such as VAMP, SNAP-25 and syntaxin are essential for intracellular trafficking, but what are their exact molecular roles and how are their interactions with other proteins manifest? Capitalizing on the differential sensitivity of SNAREs to exogenous proteases, we quantified the selective removal of identified S...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00374
更新日期:2003-05-15 00:00:00
abstract::The presence of an acetolysis-resistant polymer (sporopollenin) in the cellular slime moulds is demonstrated. This polymer is located on the stalk sheath of fruiting bodies as a bundle of fine fibrils (4-5 nm diameter). The location and structure of sporopollenin in spores are shown to vary considerably, depending upo...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::We have used the H-7w subclone of a Chinese hamster ovary cell line (K1) to investigate the role of cell surface architecture (specifically microvilli, blebs, and sheets) in determining the relative agglutinability of a cell line with Con A. Our evidence clearly demonstrates that no specific, immediately recognizable ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1978-12-01 00:00:00
abstract::Cancers arising in the oesophageal epithelium are among the most common fatal tumors in the world. Despite this, comparatively little is known about the cell biology and organization of this tissue. Recently, in vitro and in vivo techniques developed over the past 30 years for the study of the epidermis have been appl...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:
更新日期:2002-05-01 00:00:00
abstract::Sox7, Sox17 and Sox18 constitute group F of the Sox family of HMG box transcription factor genes. Dominant-negative mutations in Sox18 underlie the cardiovascular defects observed in ragged mutant mice. By contrast, Sox18(-/-) mice are viable and fertile, and display no appreciable anomaly in their vasculature, sugges...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.03081
更新日期:2006-09-01 00:00:00
abstract::The protozoan parasite Giardia lamblia has the unusual morphology of bearing two equal-sized nuclei. This organism probably represents the earliest diverging lineage of eukaryotes, suggesting that its biological tactics may be transitional. To begin to understand the role played by the two equal-sized nuclei in this o...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00