The molecular biology of desmosomes and hemidesmosomes: ?What's in a name?'
Department of Cell and Structural Biology, University of Manchester, UK. BioEssays
(Impact Factor: 4.73).
06/1992; 14(6):385-93. DOI: 10.1002/bies.950140608
Desmosomes are junctions involved in intercellular adhesion of epithelial cells and hemidesmosomes are junctions involved in adhesion of epithelia to basement membranes. Both are characterised at the ultrastructural level by dense cytoplasmic plaques which are linked to the intermediate filament cytoskeleton of the cells. The plaques strongly resemble each other suggesting a relationship between the two kinds of junctions, as implied by their names. Recent characterisation of the molecular components of the junctions shows they are, in fact, quite unrelated implying that structural similarity is fortuitous. The molecular biology raises many fascinating problems relating to their structure and function.
Available from: laminitisresearch.org
- "The adherence of the lamellar epidermal basal cells (EBCs) to the BM is dependent on the integrity of numerous attachment plaques called hemidesmosomes (HDs) (Ojeda et al. 2001). HDs are characterised at the ultrastructural level by electron dense cytoplasmic plaques and not only join epithelial cells to the BMZ, but also function as signal transducers (Borradori and Sonnenberg 1996) and connect intermediate filaments (IFs) on the cytoplasmic side of the plasma membrane with anchoring fibrils on its extracellular side (Legan et al. 1992). "
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ABSTRACT: The pathology of equine laminitis has been well-documented 48 h after dosing with oligofructose when clinical lameness and lamellar disintegration is well advanced. Further analysis of the earliest lesions, by collecting lamellar samples at the first sign of foot lameness after oligofructose dosing is required in order to increase understanding of the disease.
To investigate lamellar epidermal hemidesmosome damage and basement membrane dysadhesion by transmission electron microscopy (TEM).
Eight clinically normal, mature Standardbred horses were divided randomly into 2 groups of 4. The treatment group were dosed with oligofructose (10 g/kg bwt) and subjected to euthanasia when shifting weight from one foot to other commenced and at the first sign of lameness during walking and turning. This occurred at 24 h in 3 horses and 30 h in one. The sham treatment control group were dosed with water and subjected to euthanasia after 48 h. Lamellar tissues of the front feet were harvested and processed for ultrastructural study using TEM.
Examination by TEM showed excessive waviness of the basement membrane zone and pointed tips of some secondary epidermal lamellae, an ultrastructural lesion typical of laminitis. The average number of hemidesmosomes/microm of basement membrane was decreased and their distance from the centre of the lamina densa of the basement membrane was increased.
Laminitis lesions are detectable 24 h after oligofructose administration.
Hindgut events occurring in the first 24 h after dosing have begun the destruction of the hoof lamellar interface. Prevention and treatment strategies should precede lameness if they are to be efficacious.
Available from: James Robert Mcmillan
- "In addition to the morphometric observations, non-obliquely sectioned control desmosomes regularly showed a clearly de¢ned and distinct two-plaque structure (Fig 4g, arrowheads) comprising a cell-membrane-associated dense plaque adjacent to an electron-lucent area that, in turn, was apposed to an inner dense plaque in close association with keratin intermediate ¢laments (as described by Legan et al, 1992; Garrod, 1993; Garrod et al, 2002). The electron-dense extracellular mid-line was also more prominent in control skin than in PkP1-null skin (Fig 4g, arrows, vs Fig 4h, white arrows, respectively). "
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ABSTRACT: Recessive mutations in the desmosomal plaque protein plakophilin 1 (PkP1) underlie ectodermal dysplasia/skin fragility syndrome (MIM 604536). We undertook an immunohistochemical and quantitative electron microscopic examination of suprabasal desmosomes from 4 skin samples from 3 PkP1 deficient patients, an unaffected carrier with a PKP1 heterozygous acceptor splice site mutation and 5 healthy control subjects. Desmosomal plaque size (>50 desmosomes per individual) and frequency (>20 high power fields, HPF) were assessed. Compared with controls, desmosomes were reduced dramatically both in size (49%) and frequency (61%) in the lower suprabasal layers (LSB) in PkP1 null patients (P<0.01). In the LSB compartment of the heterozygous carrier, corresponding reductions were 37% and 20%, respectively (P<0.01). Surprisingly, the PkP1 null patient's upper suprabasal layer, (USB), desmosome size was larger (59%, P<0.01) than the control value, and showed increased desmoglein 1 and PkP2 USB staining. The USB desmosome frequency in PKP1 null patients was similar to the LSB compartment (but reduced by 43% compared to USB controls). The carrier showed no difference in the USB desmosome size and frequency compared with the controls (P>0.05). The PKP1 null patients showed poorly developed inner and outer desmosomal plaques. Thus, both the patients and unaffected carrier showed reductions in the LSB desmosome size and number; despite only PkP1 null patients exhibiting any phenotype. These findings attest to the molecular recruiting and stabilizing roles of PkP1 in desmosome formation, particularly in the LSB compartment.
Available from: Yasuo Kitajima
- "esmosomes are intercellular adhering junctions that provide the plasma membrane with anchorage sites consisting of clusters of desmosomal cadherins and several plaque proteins, for the attachment of keratin intermediate-sized filaments (KIF) (Buxton et al, 1993; Koch and Franke, 1994; Legan et al, 1992). These desmosomal cadherins consist of two major transmembrane glycoproteins, ie, the desmogleins 1 to 3 (Dsg 1, 2, and 3) and the desmocollins 1 to 3 (Dsc 1, 2, and 3). "
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ABSTRACT: To determine the assembly pathway of desmoglein 3 (Dsg3) into desmosomes and the subsequent effects of pemphigus vulgaris immunoglobulin G (PV-IgG) on such, we employed a time-lapsed labeling for FITC/Rhodamine (Rod) double-stained immunofluorescence and 5-nm/10-nm gold double-stained immunoelectron microscopy by using PV-IgG, which was confirmed to react specifically Dsg3. Cells from a human squamous cell carcinoma cell line (DJM-1) were first treated briefly with PV-IgG (3 min), then incubated in either anti-human IgG-FITC or 5-nm gold antibody-containing medium (5 min), followed by a 60-minute chase in normal medium without antibodies. The same cells were reincubated with PV-IgG medium for 3 minutes, followed by either anti-human IgG-Rod or 10-nm gold antibodies for 5 minutes. Using this method, FITC and 5-nm gold particles show the fate of Dsg3-PV-IgG complexes during the following 60-minute chase. IgG-Rod or 10-nm gold particles, which are bound during the last 5 minutes of the chase, show Dsg3 molecules newly expressed on the cell surface during the 60-minute-chase period. Initially, Dsg3 formed two types of small clusters on the nondesmosomal plasma membrane, ie, either half-desmosome-like clusters with keratin intermediate filament (KIF) attachment or simple clusters without KIF attachment. The PV-IgG binding to Dsg3 caused the internalization of the simple clusters into endosomes, but not the half-desmosome-like clusters. After the 60-minute-chase period, both types of cell surface Dsg3 clusters were labeled with only 10-nm gold, suggesting that new Dsg3 molecules were being delivered to the cell surface. Desmosomes were labeled with both 5-nm gold and 10-nm gold, whereas the half-desmosome-like clusters were labeled with only 10-nm gold, suggesting that the desmosomes themselves were not split. These results suggest that Dsg3 first forms simple clusters, followed by KIF-attachment, and then becomes integrated into desmosomes, and that PV-IgG-induced internalization of the nondesmosomal simple clusters of Dsg3 may represent the primary effects of PV-IgG on keratinocytes.
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