Pemphigus vulgaris autoantibodies induce an ER stress response DOI Open Access
Coryn L Hoffman, Navaneetha Krishnan Bharathan, Yoshitaka SHIBATA

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

Desmosomes are intercellular junctions that mediate cell-cell adhesion and essential for maintaining tissue integrity. Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease caused by autoantibodies (IgG) targeting desmoglein 3 (Dsg3), a desmosomal cadherin. PV cause desmosome disassembly loss of adhesion, but the molecular signaling pathways regulate these processes not fully understood. Using high-resolution time-lapse imaging live keratinocytes, we found ER tubules make frequent persistent contacts with internalizing Dsg3 puncta in keratinocytes treated patient IgG. Biochemical experiments demonstrated IgG activated stress pathways, including both IRE1⍺ PERK cultured keratinocytes. Further, transcripts were upregulated skin. Pharmacological inhibition protected against IgG-induced disruption keratinocyte suggesting may be important pathomechanism therapeutically targetable pathway treatment. These data support model which integrated function to serve as cell sensor skin disease.

Язык: Английский

Meeting report – Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases DOI Creative Commons
Jens Waschke, Masayuki Amagai, Christoph Becker

и другие.

Journal of Cell Science, Год журнала: 2025, Номер 138(2)

Опубликована: Янв. 15, 2025

Desmosomes are adhesive cell contacts abundant in tissues exposed to mechanical strain, such as the stratified and simple epithelia of epidermis mucous membranes, well myocardium. Besides their role cohesion, desmosomes also modulate pathways important for tissue differentiation, wound healing immune responses. Dysfunctional desmosomes, resulting from pathogenic variants genes encoding desmosomal components, autoantibodies targeting adhesion molecules or inflammation, cause life-threatening diseases arrhythmogenic cardiomyopathy pemphigus contribute pathogenesis inflammatory bowel diseases. The Alpine Desmosome Disease Meeting 2024 (ADDM 2024), held Grainau, Germany October 2024, connected international researchers basic sciences with clinical experts dermatology, cardiology, gastroenterology surgery. participants discussed recent advances, identified hot topics desmosome biology disease provided new concepts treatment approaches.

Язык: Английский

Процитировано

1

Pumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey–Hailey, and Grover Disease DOI
Robert M. Harmon, Jessica Ayers, Erin McCarthy

и другие.

Journal of Investigative Dermatology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Язык: Английский

Процитировано

4

Pemphigus vulgaris autoantibodies induce an ER stress response DOI

Coryn L. Hoffman,

Navaneetha Krishnan Bharathan, Yoshitaka SHIBATA

и другие.

Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0

Desmoplakin tail domain position in the desmosomal plaque is isoform dependent DOI Creative Commons
Collin M. Ainslie,

Krishna Patel,

Yen T. B. Tran

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract Desmoplakin (DP) is the anchoring subunit of desmosomes, macromolecular junctions that provide mechanical integrity to skin and heart. DP has three isoforms, DPI, DPIa, DPII arise from alternative splicing. The isoforms are structurally identical excluding length their central rod domain. As desmosomes complexes, precise arrangement component proteins, or architecture, essential maintain physiological function. Alterations tissue-specific expression underlies rare human diseases impacting Overall oriented with its head domain closest plasma membrane tail extending into cytosol. However, differences in architecture within desmosomal plaque remains unknown. Here, we sought define architectural each isoform. To address this, utilized direct stochastic optical reconstruction microscopy (dSTORM) analysis KO HaCaT cells stably expressing a C-terminal mEGFP tag. Our results show position isoform independent correlates length. longest rod, furthest DPII, shortest closest. We propose variable location model describe In this model, arranged domains parallel at an angle between 21° 25° membrane. These valuable insight role

Язык: Английский

Процитировано

0

Desmosome mutations in keratinocytes fuel melanoma development DOI
Patrícia A. Possik, Kerrie L. Marie, David J. Adams

и другие.

Nature Genetics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Процитировано

0

CCDC120 Phase Separation Contributes to Desmosomal Integrity and Cardiac Function DOI
Ning Huang, Hui Meng, Wei Zhao

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Abstract Desmosomes are cell-cell adhesive junctions that provide structural integrity and mechanical resistance to tissues. Disruptions in desmosome organization lead severe cardiac dermatological disorders. Emerging evidence reveals desmosomes exhibit dynamic behaviors during remodeling. However, the mechanisms initiate regulate these dynamics under physiological conditions, their correlation with desmosome-related disorders remain elusive. Here, we uncovered role of coiled-coil domain-containing 120 (CCDC120) linking desmosomal function via liquid-liquid phase separation (LLPS). CCDC120 localized was required for integrity. exhibited LLPS properties co-condensed component plakophilin-2 (PKP2) assembly, forming condensates crucial preserving structure junction stability. Moreover, were modulated by PKCα phosphorylation. Loss or impaired led intercalated disc impairment dysfunction mice. Our findings propose a model wherein orchestrates integrity, thereby establishing connections between molecular etiology dysfunction.

Язык: Английский

Процитировано

0

The Multi-kinase Inhibitor Midostaurin Mitigates Loss of Intercellular Adhesion and Skin Blistering in Pemphigus Vulgaris DOI Creative Commons
Matthias Hiermaier, Desalegn Tadesse Egu, Anna M. Sigmund

и другие.

Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Pemphigus is a group of autoimmune blistering diseases characterized by the presence autoantibodies against desmogleins, which are critical components desmosomes. These disrupt adhesive function desmosomes, leading to loss cell-cell adhesion in epidermis, manifests clinically as and erosions skin mucous membranes. Here, we explored potential use midostaurin, multi-kinase inhibitor commonly employed treatment FLT3-mutated cancers, therapeutic option for pemphigus. The results demonstrated that midostaurin effectively rescued keratin retraction induced both pemphigus vulgaris (PV) foliaceus (PF) IgG cultured keratinocytes. Additionally, prevented PV-IgG-mediated relocalization desmoglein (Dsg) 3 within cell membrane well Dsg3 on single molecule level revealed atomic force microscopy (AFM). In ex vivo human skin, successfully PV-IgG-induced blister formation. Ultrastructural analyses restored integrity findings indicate can counteract pathogenic effects autoantibodies, suggesting its agent

Язык: Английский

Процитировано

0

The desmosome as a dynamic membrane domain DOI
Stephanie E. Zimmer, Andrew P. Kowalczyk

Current Opinion in Cell Biology, Год журнала: 2024, Номер 90, С. 102403 - 102403

Опубликована: Июль 29, 2024

Язык: Английский

Процитировано

3

Pemphigus vulgaris autoantibodies induce an ER stress response DOI Open Access
Coryn L Hoffman, Navaneetha Krishnan Bharathan, Yoshitaka SHIBATA

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

Desmosomes are intercellular junctions that mediate cell-cell adhesion and essential for maintaining tissue integrity. Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease caused by autoantibodies (IgG) targeting desmoglein 3 (Dsg3), a desmosomal cadherin. PV cause desmosome disassembly loss of adhesion, but the molecular signaling pathways regulate these processes not fully understood. Using high-resolution time-lapse imaging live keratinocytes, we found ER tubules make frequent persistent contacts with internalizing Dsg3 puncta in keratinocytes treated patient IgG. Biochemical experiments demonstrated IgG activated stress pathways, including both IRE1⍺ PERK cultured keratinocytes. Further, transcripts were upregulated skin. Pharmacological inhibition protected against IgG-induced disruption keratinocyte suggesting may be important pathomechanism therapeutically targetable pathway treatment. These data support model which integrated function to serve as cell sensor skin disease.

Язык: Английский

Процитировано

0