Desmosomal junctions are abundant in epidermis and contain two classes of transmembrane glycoprotein, the desmocollins and the desmogleins, which are members of the cadherin superfamily of Ca(2+)-dependent cell adhesion molecules. The desmocollin subfamily includes DGIV/V and DGII/III while the desmoglein subfamily includes DGI, HDGC and the autoantigen of the blistering skin disease pemphigus vulgaris (PVA). There are also several non-glycosylated proteins, including the desmoplakins and plakoglobin, present in the desmosomal plaque, which forms a link between the glycoproteins and the cytokeratin intermediate filaments. To provide a picture of the expression of the desmosomal genes and their products in epidermis, we have used in situ hybridisation and immunofluorescence staining on sections of human foreskin. We find that, as expected, desmoplakin DPI/II and plakoglobin are expressed throughout the epidermis, gradually accumulating during differentiation, which probably reflects the increased numbers of desmosomes. In contrast, while keratin 14 and the hemidesmosomal component bullous pemphigoid antigen I (BPAGI) are basal-specific, desmocollin DGIV/V is expressed only in the upper spinous/granular layers of the epidermis, whereas DGII/III expression is enriched in the basal layers. Amongst the desmogleins, expression of DGI appears similar to desmoplakin and plakoglobin; PVA is more prevalent in the lower spinous layers, whereas HDGC expression is detected basally but not suprabasally. The major desmosomal cadherin transcripts are desmocollin DGIV/V and desmoglein DGI. The resultant changes in desmosomal composition and structure may reflect the maturation of desmosomes, presumably being related to the need for changes in cell adhesion during stratification, terminal differentiation, and desquamation, and point to the desmosome being a key player in epidermal differentiation.

Amagai
M.
,
Klaus-Kovtun
V.
,
Stanley
J. R.
(
1991
).
Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion.
Cell
67
,
869
877
Angst
B. D.
,
Nilles
L. A.
,
Green
K. J.
(
1990
).
Desmoplakin II expression is not restricted to stratified epithelia.
J. Cell Sci
97
,
247
257
Arnemann
J.
,
Spurr
N. K.
,
Wheeler
G. N.
,
Parker
A. E.
,
Buxton
R. S.
(
1991
).
Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP).
Genomics
10
,
640
645
Beutner
E. H.
,
Jordon
R. E.
,
Chorzelski
T. P.
(
1968
).
The immunopathology of pemphigus and bullous pemphigoid.
J. Invest. Dermatol
51
,
63
80
Bosch
F. X.
,
Leube
R. E.
,
Achtstatter
T.
,
Moll
R.
,
Franke
W. W.
(
1988
).
Expression of simple epithelial type cytokeratins in stratified epithelia as detected by immunolocalization and hybridization in situ.
J. Cell Biol
106
,
1635
1648
Burge
S. M.
(
1989
).
Darier's disease, keratins and proteases: a review.
J. R. Soc. Med
82
,
673
676
Burge
S. M.
,
Garrod
D. R.
(
1991
).
An immunohistological study of desmosomes in Darier's disease and Hailey-Hailey disease.
Br. J. Dermatol
124
,
242
251
Burge
S. M.
,
Millard
P. R.
,
Wojnarowska
F.
(
1991
).
Hailey-Hailey disease: a widespread abnormality of cell adhesion.
Br. J. Dermatol
124
,
329
332
Burge
S. M.
,
Millard
P. R.
,
Wojnarowska
F.
,
Ryan
T. J.
(
1990
).
Darier's disease: a focal abnormality of cell adhesion.
J. Cutan. Pathol
17
,
160
164
Butz
S.
,
Stappert
J.
,
Weissig
H.
,
Kemler
R.
(
1992
).
Plakoglobin and beta-catenin-distinct but closely related.
Science
257
,
1142
1144
Buxton
R. S.
,
Magee
A. I.
(
1992
).
Structure and interactions of desmosomal and other cadherins.
Semin. Cell Biol
3
,
157
167
Chapman
S. J.
,
Walsh
A.
(
1990
).
Desmosomes, corneosomes and desquamation. An ultrastructural study of adult pig epidermis.
Arch. Dermatol. Res
282
,
304
310
Chirgwin
J. M.
,
Przybyla
A. E.
,
MacDonald
R. J.
,
Rutter
W. J.
(
1979
).
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
Biochemistry
18
,
5294
5299
Collins
J. E.
,
Legan
P. K.
,
Kenny
T. P.
,
MacGarvie
J.
,
Holton
J. L.
,
Garrod
D. R.
(
1991
).
Cloning and sequence analysis of desmosomal glycoprotein 2 and glycoprotein 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains.
J. Cell Biol
113
,
381
391
Cowin
P.
,
Kapprell
H. P.
,
Franke
W. W.
(
1985
).
The complement of desmosomal plaque proteins in different cell types.
J. Cell Biol
101
,
1442
1454
Dieckmann
C. L.
,
Tzagoloff
A.
(
1985
).
Assembly of the mitochondrial membrane system. CBP6, a yeast nuclear gene necessary for synthesis of cytochrome b.
J. Biol. Chem
260
,
1513
1520
Eichner
R.
,
Sun
T.-T.
,
Aebi
U.
) (
1986
).
The role of keratin subfamilies and keratin pairs in the formation of human epidermal intermediate filaments.
J. Cell Biol
102
,
1767
1777
Franke
W. W.
,
Cowin
P.
,
Schmelz
M.
,
Kapprell
H. P.
(
1987
).
The desmosomal plaque and the cytoskeleton.
Ciba Found. Symp
125
,
26
48
Franke
W. W.
,
Goldschmidt
M. D.
,
Zimbelmann
R.
,
Mueller
H. M.
,
Schiller
D. L.
,
Cowin
P.
(
1989
).
Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein.
Proc. Nat. Acad. Sci. USA
86
,
4027
4031
Fuchs
E.
(
1990
).
Epidermal differentiation-the bare essentials.
J. Cell Biol
111
,
2807
2814
Giudice
G. J.
,
Cohen
S. M.
,
Patel
N. H.
,
Steinberg
M. S.
(
1984
).
Immunological comparison of desmosomal components from several bovine tissues.
J. Cell. Biochem
26
,
35
45
Goodwin
L.
,
Hill
J. E.
,
Raynor
K.
,
Raszi
L.
,
Manabe
M.
,
Cowin
P.
(
1990
).
Desmoglein shows extensive homology to the cadherin family of cell adhesion molecules.
Biochem. Biophys. Res. Commun
173
,
1224
1230
Green
K. J.
,
Parry
D. A.
,
Steinert
P. M.
,
Virata
M. L.
,
Wagner
R. M.
,
Angst
B. D.
,
Nilles
L. A.
(
1990
).
Structure of the human desmoplakins. Implications for function in the desmosomal plaque.
J. Biol. Chem
265
,
2603
2612
Hieda
Y.
,
Tsukita
S.
,
Tsukita
S.
(
1989
).
A new high molecular mass protein showing unique localization in desmosomal plaque.
J. Cell Biol
109
,
1511
1518
Jones
J. C.
,
Vikstrom
K. L.
,
Goldman
R. D.
(
1987
).
Evidence for heterogeneity in the 160/16510 3 M rglycoprotein components of desmosomes.
J. Cell Sci
88
,
513
520
Kapprell
H. P.
,
Owaribe
K.
,
Franke
W. W.
(
1988
).
Identification of a basic protein of M r75,000 as an accessory desmosomal plaque protein in stratified and complex epithelia.
J. Cell Biol
106
,
1679
1691
King
I. A.
,
Magee
A. I.
,
Rees
D. A.
,
Buxton
R. S.
(
1991
).
Keratinization is associated with the expression of a new protein related to the desmosomal cadherins DGII/III.
FEBS Lett
286
,
9
12
King
I. A.
,
Tabiowo
A.
,
Fryer
P. R.
(
1987
).
Evidence that major 78–44-kD concanavalin A-binding glycopolypeptides in pig epidermis arise from the degradation of desmosomal glycoproteins during terminal differentiation.
J. Cell Biol
105
,
3053
3063
King
I. A.
,
Wood
M. J.
,
Fryer
P. R.
(
1989
).
Desmoglein II-derived glycopeptides in human epidermis.
J. Invest. Dermatol
92
,
22
26
Klein-Szanto
A. J. P.
(
1977
).
Stereologic baseline data of normal human epidermis.
J. Invest. Dermatol
68
,
73
78
Koch
P. J.
,
Goldschmidt
M. D.
,
Walsh
M. J.
,
Zimbelmann
R.
,
Franke
W. W.
(
1991
).
Complete amino acid sequence of the epidermal desmoglein precursor polypeptide and identification of a second type of desmoglein gene.
Eur. J. Cell Biol
55
,
200
208
Koch
P. J.
,
Goldschmidt
M. D.
,
Walsh
M. J.
,
Zimbelmann
R.
,
Schmelz
M.
,
Franke
W. W.
(
1991
).
Amino acid sequence of bovine muzzle epithelial desmocollin derived from cloned cDNA: a novel subtype of desmosomal cadherins.
Differentiation
47
,
29
36
Koch
P. J.
,
Goldschmidt
M. D.
,
Zimbelmann
R.
,
Troyanovsky
R.
,
Franke
W. W.
(
1992
).
Complexity and expression patterns of the desmosomal cadherins.
Proc. Nat. Acad. Sci. USA
89
,
353
357
Koch
P. J.
,
Walsh
M. J.
,
Schmelz
M.
,
Goldschmidt
M. D.
,
Zimbelmann
R.
,
Franke
W. W.
(
1990
).
Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules.
Eur. J. Cell Biol
53
,
1
12
Korman
N. J.
(
1990
).
Pemphigus.
Dermatol. Clin
8
,
689
700
Koulu
L.
,
Kusumi
A.
,
Steinberg
M. S.
,
Klaus-Kovtun
V.
,
Stanley
J. R.
(
1984
).
Human autoantibodies against a desmosomal core protein in pemphigus foliaceus.
J. Exp. Med
160
,
1509
1518
Magee
A. I.
,
Buxton
R. S.
(
1991
).
Transmembrane molecular assemblies regulated by the greater cadherin family.
Curr. Opin. Cell Biol
3
,
854
861
McCrea
P. D.
,
Turck
C. W.
,
Gumbiner
B.
(
1991
).
A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin.
Science
254
,
1359
1361
Mechanic
S.
,
Raynor
K.
,
Hill
J. E.
,
Cowin
P.
(
1991
).
Desmocollins form a subset of the cadherin family of cell adhesion molecules.
Proc. Nat. Acad. Sci. USA
88
,
4476
4480
Moll
R.
,
Franke
W. W.
,
Schiller
D. L.
,
Geiger
B.
,
Krepler
R.
(
1982
).
The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells.
Cell
31
,
11
24
Mutasim
D. F.
,
Takahashi
Y.
,
Labib
R. S.
,
Anhalt
G. J.
,
Patel
H. P.
,
Diaz
L. A.
(
1985
).
A pool of bullous pemphigoid antigen(s) is intracellular and associated with the basal cell cytoskeleton-hemidesmosome complex.
J. Invest. Dermatol
84
,
47
53
Nelson
W. G.
,
Sun
T.-T.
(
1983
).
The 50-and 58-kdalton keratin classes as molecular markers for stratified squamous epithelia: cell culture studies.
J. Cell Biol
97
,
244
251
Nilles
L. A.
,
Parry
D. A. D.
,
Powers
E. E.
,
Angst
B. D.
,
Wagner
R. M.
,
Green
K. J.
(
1991
).
Structural analysis and expression of human desmoglein: a cadherin-like component of the desmosome.
J. Cell Sci
99
,
809
821
Parker
A. E.
,
Wheeler
G. N.
,
Arnemann
J.
,
Pidsley
S. C.
,
Ataliotis
P.
,
Thomas
C. L.
,
Rees
D. A.
,
Magee
A. I.
,
Buxton
R. S.
(
1991
).
Desmosomal glycoproteins II and III: cadherin-like junctional molecules generated by alternative splicing.
J. Biol. Chem
266
,
10438
10445
Parrish
E. P.
,
Garrod
D. R.
,
Mattey
D. L.
,
Hand
L.
,
Steart
P. V.
,
Weller
R. O.
(
1986
).
Mouse antisera specific for desmosomal adhesion molecules of suprabasal skin cells, meninges, and meningioma.
Proc. Nat. Acad. Sci. USA
83
,
2657
2661
Peifer
M.
,
McCrea
P. D.
,
Green
K. J.
,
Wieschaus
E.
,
Gumbiner
B. M.
(
1992
).
The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties.
J. Cell Biol
118
,
681
691
Penn
E. J.
,
Hobson
C.
,
Rees
D. A.
,
Magee
A. I.
(
1987
).
Structure and assembly of desmosome junctions: biosynthesis, processing, and transport of the major protein and glycoprotein components in cultured epithelial cells.
J. Cell Biol
105
,
57
68
Regnier
M.
,
Vaigot
P.
,
Michel
S.
,
Prunieras
M.
(
1985
).
Localization of bullous pemphigoid antigen (BPA) in isolated human keratinocytes.
J. Invest. Dermatol
85
,
187
190
Schwarz
M. A.
,
Owaribe
K.
,
Kartenbeck
J.
,
Franke
W. W.
(
1990
).
Desmosomes and hemidesmosomes: constitutive molecular components.
Annu. Rev. Cell. Biol
6
,
461
491
Skerrow
C. J.
,
Clelland
D. G.
,
Skerrow
D.
(
1989
).
Changes to desmosomal antigens and lectin-binding sites during differentiation in normal human epidermis: a quantitative ultrastructural study.
J. Cell Sci
92
,
667
677
Stanley
J. R.
,
Koulu
L.
,
Klaus-Kovtun
V.
,
Steinberg
M. S.
(
1986
).
A monoclonal antibody to the desmosomal glycoprotein desmoglein I binds the same polypeptide as human autoantibodies in pemphigus foliaceus.
J. Immunol
136
,
1227
1230
Suhrbier
A.
,
Garrod
D.
(
1986
).
An investigation of the molecular components of desmosomes in epithelial cells of five vertebrates.
J. Cell Sci
81
,
223
242
Tyner
A. L.
,
Fuchs
E.
(
1986
).
Evidence for posttranscriptional regulation of the keratins expressed during hyperproliferation and malignant transformation in human epidermis.
J. Cell Biol
103
,
1945
1955
Westgate
G. E.
,
Weaver
A. C.
,
Couchman
J. R.
(
1985
).
Bullous pemphigoid antigen localization suggests an intracellular association with hemidesmosomes.
J. Invest. Dermatol
84
,
218
224
Wheeler
G. N.
,
Buxton
R. S.
,
Parker
A. E.
,
Arnemann
J.
,
Rees
D. A.
,
King
I. A.
,
Magee
A. I.
(
1991
).
Desmosomal glycoproteins I, IIand III: novel members of the cadherin superfamily.
Biochem. Soc. Trans
19
,
1060
1064
Wheeler
G. N.
,
Parker
A. E.
,
Thomas
C. L.
,
Ataliotis
P.
,
Poynter
D.
,
Arnemann
J.
,
Rutman
A. J.
,
Pidsley
S. C.
,
Watt
F. M.
,
Rees
D. A.
,
Buxton
R. S.
,
Magee
A. I.
(
1991
).
Desmosomal glycoprotein I, a component of intercellular desmosome junctions, is related to the cadherin family of cell adhesion molecules.
Proc. Nat. Acad. Sci. USA
88
,
4796
4800
White
F. H.
,
Gohari
K.
(
1984
).
Some aspects of desmosomal morphology during differentiation of hamster cheek pouch epithelium.
J. Submicrosc. Cytol
16
,
407
422
This content is only available via PDF.