Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains.

Collins, Jane; Legan, P. Kevin; Kenny, Tp; MacGarvie, Jennie; Holton, JL; Garrod, David R.

doi:10.1083/jcb.113.2.381

Cited by 183 publications

(95 citation statements)

References 68 publications

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“…All three desmocollin gene products undergo alternative splicing, resulting in the generation of the Dsc "a" form and a shorter Dsc "b" form of the proteins, which differ in the length of their respective carboxy-terminal domains ( Fig. 2) (Collins et al 1991;Parker et al 1991). Evolutionarily and structurally, the desmocollin genes are more closely related to the classical cadherins (i.e., E-and N-cadherin) than they are to the desmogleins (Kljuic et al 2004).…”

Section: The Desmosomal Cadherins Desmogleins and Desmocollins: Strucmentioning

confidence: 99%

The Desmosome

Delva¹,

Tucker²,

Kowalczyk³

2009

Cold Spring Harbor Perspectives in Biology

348

310

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Section: The Desmosomal Cadherins Desmogleins and Desmocollins: Strucmentioning

confidence: 99%

The Desmosome

Delva¹,

Tucker²,

Kowalczyk³

2009

Cold Spring Harbor Perspectives in Biology

348

310

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“…Desmocollins are subjected to alternative splicing resulting in two isoforms that differ in the length of their cytoplasmic domains (37,38). After induction of apoptosis both the 109-kDa and the 100-kDa splice variants of Dsc3 were cleaved within 24 h (Fig.…”

Section: Cleavage Of Desmoglein-3 and Desmocollin-3 Duringmentioning

confidence: 99%

The Fate of Desmosomal Proteins in Apoptotic Cells

Weiske¹,

Schöneberg²,

Schröder³

et al. 2001

Journal of Biological Chemistry

121

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Activation of caspases results in the disruption of structural and signaling networks in apoptotic cells. Recent biochemical and cell biological studies have shown that components of the cadherin-catenin adhesion complex in epithelial adherens junctions are targeted by caspases during apoptosis. In epithelial cells, desmosomes represent a second type of anchoring junctions mediating strong cell-cell contacts. Using antibodies directed against a set of desmosomal proteins, we show that desmosomes are proteolytically targeted during apoptosis. Desmogleins and desmocollins, representing desmosome-specific members of the cadherin superfamily of cell adhesion molecules, are specifically cleaved after onset of apoptosis. Similar to E-cadherin, the desmoglein-3 cytoplasmic tail is cleaved by caspases. In addition the extracellular domains of desmoglein-3 and desmocollin-3 are released from the cell surface by a metalloproteinase activity. In the presence of caspase and/or metalloproteinase inhibitors, both cleavage reactions are almost completely inhibited. As reported previously, the desmosomal plaque protein plakoglobin is cleaved by caspase-3 during apoptosis. Our studies now show that plakophilin-1 and two other major plaque proteins, desmoplakin-1 and -2, are also cleaved by caspases. Immunofluorescence analysis confirmed that this cleavage results in the disruption of the desmosome structure and thus contributes to cell rounding and disintegration of the intermediate filament system. Apoptosis is a highly conserved process important for the destruction of excess or damaged cells during the development and in the homeostasis of multicellular organisms (1). Impaired regulation of programmed cell death is involved in the pathogenesis of cancer and immune and neuronal diseases (2, 3). Once the cell death program is started, dramatic changes in cell morphology can be observed such as nuclear/cytoplasmic condensation, formation of membrane protrusions, DNA fragmentation, and disruption of the structural integrity followed by fragmentation into "apoptotic bodies" that are removed by subsequent engulfment by neighboring cells or macrophages. Many of these morphological changes can be attributed to the cleavage of structural and regulatory proteins by members of the caspase family of cysteine proteinases. Caspases specifically cleave substrate proteins C-terminal to aspartate residues (for review see Refs. 4 -6). Caspase-3-mediated cleavage of inhibitor of caspase-activated DNase releases caspase-activated DNase, which is responsible for the generation of the nucleosomal ladder. Cleavage of cytoskeletal proteins and regulators such as fodrin (7), gelsolin (8), Gas2 (9), and focal adhesion kinase (10 -12) and adhesion molecules such as cadherins (13-16) results in disruption of the cyto-architecture.Desmosomes are punctate intercellular junctions located on the basolateral side primarily of epithelial cells. They provide mechanical strength to epithelial tissues by forming stable cell-cell contacts that are anchored to the...

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“…In particular, the COOH-terminal region of desmoglein contains a proline-rich linker region, a series of short (~29 amino acids long) repeats and a glycine-rich terminal domain (Garrod and Chidgey, 2008;Holthofer et al, 2007), which likely mediates weak interactions with other desmosomal proteins (Kami et al, 2009). Conversely, alternative splicing within the COOH-terminus of desmocollin gives rise to two forms (Collins et al, 1991;Parker et al, 1991); the "b" or shorter form does not contain the traditional catenin-binding domain, however, the longer "a" form possesses a normal catenin-binding domain and has been shown to bind plakoglobin with high affinity (Troyanovsky et al, 1993). Many studies suggest that both desmoglein and desmocollin are necessary for desmosomal formation (Getsios et al, 2004;Marcozzi et al, 1998;Tselepis et al, 1998).…”

Section: Desmosomal Cadherinsmentioning

confidence: 99%