Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease

Megumi Hakuno, H. Shimizu, M. Akiyama, Masayuki Amagai, J. K. Wahl, M. J. Wheelock, T. Nishikawa

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

In order to clarify the pathomechanism of acantholysis in Hailey-Hailey disease (HHD) and Darier's disease (DD), the distribution of desmosomal and adherens junction-associated proteins was studied in the skin of patients with HHD (n = 4) and DD (n = 3). Domain-specific antibodies were used to determine the cellular localization of the desmosomal transmembrane glycoproteins (desmogleins 1 and 3 and desmocollin), desmosomal plaque proteins (desmoplakin, plakophilin and plakoglobin) and adherens junction- associated proteins (E-cadherin, α-catenin, β-catenin and actin). A significant difference in staining patterns between intra- and extracellular domains of desmosomal cadherins and E-cadherin was demonstrated in acantholytic cells in both HHD and DD, but not in those in pemphigus vulgaris and pemphigus foliaceus samples used as controls. In acantholytic cells in HHD and DD, antibodies against attachment plaque proteins and intracellular epitopes of desmosomal cadherins exhibited diffuse cytoplasmic staining, whereas markedly reduced staining was observed with antibodies against extracellular epitopes of the desmogleins. Similarly, membrane staining of an intracellular epitope of E-cadherin was preserved, while immunoreactivity of an extracellular epitope of E-cadherin was destroyed. While the DD gene has been identified as ATP2A2, the gene for HHD has not been clarified. The dissociation of intra- and extracellular domains of desmosomal cadherin and E-cadherin is characteristic of the acantholytic cells in HHD and DD, and not of pemphigus. This common phenomenon in HHD and DD might be closely related to the pathophysiological mechanisms in both conditions.

Original languageEnglish
Pages (from-to)702-711
Number of pages10
JournalBritish Journal of Dermatology
Volume142
Issue number4
DOIs
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Desmosomal Cadherins
Benign Familial Pemphigus
Darier Disease
Cadherins
Pemphigus
Epitopes
Staining and Labeling
Adherens Junctions
Catenins
Antibodies
Plakophilins
Proteins
Desmocollins
Desmogleins
Desmoglein 3
Desmoglein 1
Desmoplakins
Acantholysis
gamma Catenin
Intracellular Membranes

Keywords

  • Adherens junction
  • Cell adhesion molecule
  • Desmocollin
  • Desmoglein
  • Desmosome
  • Familial benign chronic pemphigus

ASJC Scopus subject areas

  • Dermatology

Cite this

Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease. / Hakuno, Megumi; Shimizu, H.; Akiyama, M.; Amagai, Masayuki; Wahl, J. K.; Wheelock, M. J.; Nishikawa, T.

In: British Journal of Dermatology, Vol. 142, No. 4, 2000, p. 702-711.

Research output: Contribution to journalArticle

Hakuno, Megumi ; Shimizu, H. ; Akiyama, M. ; Amagai, Masayuki ; Wahl, J. K. ; Wheelock, M. J. ; Nishikawa, T. / Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease. In: British Journal of Dermatology. 2000 ; Vol. 142, No. 4. pp. 702-711.
@article{d08725782553424180e58c7fbd2d06c8,
title = "Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease",
abstract = "In order to clarify the pathomechanism of acantholysis in Hailey-Hailey disease (HHD) and Darier's disease (DD), the distribution of desmosomal and adherens junction-associated proteins was studied in the skin of patients with HHD (n = 4) and DD (n = 3). Domain-specific antibodies were used to determine the cellular localization of the desmosomal transmembrane glycoproteins (desmogleins 1 and 3 and desmocollin), desmosomal plaque proteins (desmoplakin, plakophilin and plakoglobin) and adherens junction- associated proteins (E-cadherin, α-catenin, β-catenin and actin). A significant difference in staining patterns between intra- and extracellular domains of desmosomal cadherins and E-cadherin was demonstrated in acantholytic cells in both HHD and DD, but not in those in pemphigus vulgaris and pemphigus foliaceus samples used as controls. In acantholytic cells in HHD and DD, antibodies against attachment plaque proteins and intracellular epitopes of desmosomal cadherins exhibited diffuse cytoplasmic staining, whereas markedly reduced staining was observed with antibodies against extracellular epitopes of the desmogleins. Similarly, membrane staining of an intracellular epitope of E-cadherin was preserved, while immunoreactivity of an extracellular epitope of E-cadherin was destroyed. While the DD gene has been identified as ATP2A2, the gene for HHD has not been clarified. The dissociation of intra- and extracellular domains of desmosomal cadherin and E-cadherin is characteristic of the acantholytic cells in HHD and DD, and not of pemphigus. This common phenomenon in HHD and DD might be closely related to the pathophysiological mechanisms in both conditions.",
keywords = "Adherens junction, Cell adhesion molecule, Desmocollin, Desmoglein, Desmosome, Familial benign chronic pemphigus",
author = "Megumi Hakuno and H. Shimizu and M. Akiyama and Masayuki Amagai and Wahl, {J. K.} and Wheelock, {M. J.} and T. Nishikawa",
year = "2000",
doi = "10.1046/j.1365-2133.2000.03415.x",
language = "English",
volume = "142",
pages = "702--711",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Dissociation of intra- and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease

AU - Hakuno, Megumi

AU - Shimizu, H.

AU - Akiyama, M.

AU - Amagai, Masayuki

AU - Wahl, J. K.

AU - Wheelock, M. J.

AU - Nishikawa, T.

PY - 2000

Y1 - 2000

N2 - In order to clarify the pathomechanism of acantholysis in Hailey-Hailey disease (HHD) and Darier's disease (DD), the distribution of desmosomal and adherens junction-associated proteins was studied in the skin of patients with HHD (n = 4) and DD (n = 3). Domain-specific antibodies were used to determine the cellular localization of the desmosomal transmembrane glycoproteins (desmogleins 1 and 3 and desmocollin), desmosomal plaque proteins (desmoplakin, plakophilin and plakoglobin) and adherens junction- associated proteins (E-cadherin, α-catenin, β-catenin and actin). A significant difference in staining patterns between intra- and extracellular domains of desmosomal cadherins and E-cadherin was demonstrated in acantholytic cells in both HHD and DD, but not in those in pemphigus vulgaris and pemphigus foliaceus samples used as controls. In acantholytic cells in HHD and DD, antibodies against attachment plaque proteins and intracellular epitopes of desmosomal cadherins exhibited diffuse cytoplasmic staining, whereas markedly reduced staining was observed with antibodies against extracellular epitopes of the desmogleins. Similarly, membrane staining of an intracellular epitope of E-cadherin was preserved, while immunoreactivity of an extracellular epitope of E-cadherin was destroyed. While the DD gene has been identified as ATP2A2, the gene for HHD has not been clarified. The dissociation of intra- and extracellular domains of desmosomal cadherin and E-cadherin is characteristic of the acantholytic cells in HHD and DD, and not of pemphigus. This common phenomenon in HHD and DD might be closely related to the pathophysiological mechanisms in both conditions.

AB - In order to clarify the pathomechanism of acantholysis in Hailey-Hailey disease (HHD) and Darier's disease (DD), the distribution of desmosomal and adherens junction-associated proteins was studied in the skin of patients with HHD (n = 4) and DD (n = 3). Domain-specific antibodies were used to determine the cellular localization of the desmosomal transmembrane glycoproteins (desmogleins 1 and 3 and desmocollin), desmosomal plaque proteins (desmoplakin, plakophilin and plakoglobin) and adherens junction- associated proteins (E-cadherin, α-catenin, β-catenin and actin). A significant difference in staining patterns between intra- and extracellular domains of desmosomal cadherins and E-cadherin was demonstrated in acantholytic cells in both HHD and DD, but not in those in pemphigus vulgaris and pemphigus foliaceus samples used as controls. In acantholytic cells in HHD and DD, antibodies against attachment plaque proteins and intracellular epitopes of desmosomal cadherins exhibited diffuse cytoplasmic staining, whereas markedly reduced staining was observed with antibodies against extracellular epitopes of the desmogleins. Similarly, membrane staining of an intracellular epitope of E-cadherin was preserved, while immunoreactivity of an extracellular epitope of E-cadherin was destroyed. While the DD gene has been identified as ATP2A2, the gene for HHD has not been clarified. The dissociation of intra- and extracellular domains of desmosomal cadherin and E-cadherin is characteristic of the acantholytic cells in HHD and DD, and not of pemphigus. This common phenomenon in HHD and DD might be closely related to the pathophysiological mechanisms in both conditions.

KW - Adherens junction

KW - Cell adhesion molecule

KW - Desmocollin

KW - Desmoglein

KW - Desmosome

KW - Familial benign chronic pemphigus

UR - http://www.scopus.com/inward/record.url?scp=0034092661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034092661&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2133.2000.03415.x

DO - 10.1046/j.1365-2133.2000.03415.x

M3 - Article

VL - 142

SP - 702

EP - 711

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 4

ER -