Desmoglein Endocytosis and Desmosome Disassembly Are Coordinated Responses to Pemphigus Autoantibodies*

@article{Calkins2006DesmogleinEA,
  title={Desmoglein Endocytosis and Desmosome Disassembly Are Coordinated Responses to Pemphigus Autoantibodies*},
  author={Cathárine C. Calkins and Shannon V Setzer and Jean Marie Jennings and Susan Summers and Kazuyuki Tsunoda and Masayuki Amagai and Andrew P. Kowalczyk},
  journal={Journal of Biological Chemistry},
  year={2006},
  volume={281},
  pages={7623 - 7634}
}
Desmosomes are adhesive intercellular junctions prominent in the skin and heart. Loss of desmosome function is associated with severe congenital and acquired disorders characterized by tissue fragility. Pemphigus vulgaris (PV) is an autoimmune disorder in which antibodies are directed against the desmosomal adhesion molecule Dsg3, resulting in severe mucosal erosions and epidermal blistering. To define the mechanisms by which Dsg3 autoantibodies disrupt keratinocyte adhesion, the fate of PV IgG… 

Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies.

TLDR
Immunofluorescence and ELISA studies indicate that pathogenic PV mAbs specifically cause internalization of newly synthesized Dsg3 during desmosome assembly, correlating with their pathogenic activity.

Keratin Retraction and Desmoglein3 Internalization Independently Contribute to Autoantibody-Induced Cell Dissociation in Pemphigus Vulgaris

Pemphigus vulgaris (PV) is a potentially lethal autoimmune disease characterized by blister formation of the skin and mucous membranes and is caused by autoantibodies against desmoglein (Dsg) 1 and

Desmosome disassembly in response to pemphigus vulgaris IgG occurs in distinct phases and can be reversed by expression of exogenous Dsg3.

TLDR
Analysis of primary human keratinocytes and patient IgG support a model in which PV IgG cause the loss of cell adhesion by altering the dynamics of Dsg3 assembly into desmosomes and the turnover of cell surface pools of DSG3 through endocytic pathways.

p38MAPK Signaling and Desmoglein-3 Internalization Are Linked Events in Pemphigus Acantholysis*

TLDR
The data suggest that p38MAPK is capable of regulating PV IgG-mediated DSG3 internalization and that previously isolated mechanistic observations may be linked to a common pathway by which pemphigus autoantibodies lead to acantholysis.

Loss of Desmoglein Binding Is Not Sufficient for Keratinocyte Dissociation in Pemphigus.

TLDR
Results demonstrate that inhibition of Dsg3 binding is not sufficient to cause loss of cell cohesion, but rather alters signaling events which, in lipid raft-dependent manner, induce cell dissociation.

Keratins Regulate p38MAPK-Dependent Desmoglein Binding Properties in Pemphigus

TLDR
It is concluded that p38MAPK signaling is (i) critical for regulation of cell adhesion, (ii) regulated by keratins, and (iii) targets both keratin-dependent and -independent mechanisms.

Plakophilin-1 protects keratinocytes from pemphigus vulgaris IgG by forming calcium-independent desmosomes

TLDR
It is reported that enhanced expression of PKP-1 protects keratinocytes from PV IgG-induced loss of cell-cell adhesion and transforms desmosome adhesion from a calcium-dependent to acium-independent and hyper-adhesive state.

Super-resolution microscopy reveals altered desmosomal protein organization in pemphigus vulgaris patient tissue

TLDR
Findings indicate that Dsg3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in PV patient tissue, and reveals that super-resolution optical imaging is powerful approach for studying epidermal adhesion structures in normal and diseased skin.

150th Anniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

TLDR
Pemphigus could be referred to a “desmosome-remodeling disease involving pemPHigus IgG-activated outside-in signaling events”, which may explain different clinical (non-inflammatory, inflammatory, and necrolytic) types of pemphIGus.

Internalization of Non-Clustered Desmoglein 1 without Depletion of Desmoglein 1 from Adhesion Complexes in An Experimental Model of the Autoimmune Disease Pemphigus Foliaceus

TLDR
Investigation of changes in subcellular distribution of Dsg1 in response to serum of patients with PF by using an in vitro model of PF suggests that anti-Dsg1 antibodies from PF serum could cause the internalization of non-clustered Dsg 1 and perturb the formation of new desmosomes but not directly disrupt Dsg2-containing junctions when stable contacts are already formed.
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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