Desmosomes and hemidesmosomes

David R. Garrod

University of Manchester, Manchester, UK

Desmosomes and hemidesmosomes are extremely different in their

molecular composition. Most of the protein and glycoprotein components
are products of members of multigene families, but show specialization
for plaque formation and intermediate filament attachment. Desmosomal
glycoproteins are more heterogeneous than previously suspected, with
different isoforms showing tissue-specific and differentiation-related expres-
sion. Both types of junctions can be modulated in response to extra-
cellular signals and may turn out to be involved in signal transduction.

Current Opinion in Cell Biology 1993, 5:30-40

Introduction tissue locations. Sequence data now confirm that both

Desmosomes are intercellular junctions that mediate
strong adhesion between cells in epithelia, cardiac mus-
cle, pia and arachnoid meninges, and follicular den-
dritic cells. Hemidesmosomes are junctions that medi-
ate adhesion to the <basement membrane in some epi-
thelia (e.g. epidermis, bladder, trachea, breast and am-
nion). These junctions have related names because they
display common ultrastructural features; both possess
dense, membrane-associated cytoplasmic plaques linked
to intermediate tilaments (IFS; Fig. 1). Elucidation of
molecular composition has conclusively demonstrated
that desmosomes and hemidesmosomes are analogous
rather than homologous structures, their cytoplasmic
plaque components and adhesion glycoproteins being
quite distinct (Table 1; reviewed in [la] >. There have
been significant new developments in the understanding
of both junctional types with important implications for
their respective roles in tissue structure, development and
disease. Because they are so different in molecular com-
position, it will be convenient to discuss them separately.
Desmosomes
Desmosomal glycoproteins: multigene cadherin
subfamilies
Cloning and sequencing of the major desmosomal
glycoproteins, desmoglein and the desmocollins, from
bovine and human sources has shown them to belong
to the cadherin family of calcium-dependent adhesion
molecules (Fig. 2). The subject has been covered by
several groups and has been recently reviewed [1*,2-l.
Antibody reactivity patterns previously suggested hetero-
geneity among desmosomal glycoproteins in different
desmogleins and desmocollins occur as different iso-
forms that constitute (as yet) small subfamilies within
the cadherin superfamily. The desmoglein subfamily has
three members. Desmoglein (DGl), first cloned from
bovine and human sources by several groups [3-6], has
the structure indicated in Fig. 2. Human desmoglein from
colon, from which a partial carboxyl-terminal sequence
was obtained from colon carcinoma cells, shows only
29 % identity with DGl [7*]. Pemphigus vulgaris antigen
(PVA) is clearly a member of this subfamily because of
sequence homology, but differs from desmoglein in two
respects [@*I: first, it has five complete cadherin-like ex-
tracellular domains resembling desmocollins and other
cadherins, rather than the four cadherin-like domains
and short membrane-proximal domain of desmoglein
(Fig. 2); second, it has a shorter cytoplasmic region than
desmoglein, lacking two of the five cytoplasmic repeats
(RUD in Fig. 2) and the carboxyl-terminal glycine-rich
domain.
The bovine desmocollin subfamily consists of three iso-
forms, types 1, 2 and 3, which are the products of differ-
ent genes. Types 1 and 2 each exist as a pair of proteins
of different sizes generated by alternative splicing (Fig.
2) [9]. In each case, the larger protein is called desmo-
collin I and the smaller, desmocollin II (Table 1; Fig. 2).
Heterogeneity of bovine desmocollins was demonstrated
by determination of a seqence from bovine nasal epi-
dermis, which showed 46 % identity at the amino acid
level in the first published sequence [lo-]. The original
sequence was designated type 1 and the new sequence
type 2. Type 3 bovine desmocollin was identified from a
partial sequence of the transmembrane and cytoplasmic
regions and shows 55 % and 72 % identity with types 1
and 2, respectively (PK Legan, DR Garrod, unpublished
data). Type 3 probably also exists in alternatively spliced
forms, but we do not yet have direct evidence for this.

Abbreviations
BPACibullous pemphigoid antigen; IF-intermediate filament; PVA-pemphigus vulgaris antigen.

30 @ current Biology Ltd ISSN 0955-0674

 Desmosomes and hemidesmosomes Garrod 31

Intracellular

Intermediate
filament

.Satellite
T.~;~que . .._._______ A zone
Desmoglein
Desmocollins . . . Mid-line .Intercellular
J space

Intracellular

(b)

BPAGl 200 kD c 1:. ] Inner plaque

c.
oH34, P,asma membrane

lamina lucida
tarnina densa

tilament
\ Anchoring Extracellular
fibril

Fig. 1. The principal ultrastructural features of (a) the desmosome and fb) the hemidesmosome. Both structures are roughly circular
membrane organelles, usually less than 1 pm in diameter. The locations of some of the major glycoprotein and protein components as
suggested by immuno-electron microscopy are indicated. Adapted from [lo].

The human desmocollin family so far consists of two
alternatively spliced isoform pairs, DGII/III and DGIV/V.
Human gene names have been designated and chromo-
somal locations assigned(Table 2) [2-0,1l-131. The de-
duced amino acid sequence of DGII/III [ 141 shows 77 %
identity with bovine type 2 and 79 % identity with the par-
tial sequenceof bovine type 3, so it is not yet clear which
are the true species homologues. DGIVIII and bovine
type 1 show only 53 % identity. The small amount of
protein sequence published for DGIV/V [IS*] suggests
that it may be the homologue of bovine type 1.
The bovine desmocollin isoforms show tissue-specific
expression. Expression of the different isoforms has
been located through the use of polymerase chain reac-
tion and northern blotting data: type 1 in epidermis and
tongue epithelium; type 2 in stratified, complex and sim-
ple epithelia and heart; and type 3 in epidermis, tongue,
oesophagus and stomach epithelia (PK Legan, DR Gar-
rod, unpublished data; [lo=]). Thus, all three types are
expressed in epidermis. There is now evidence to sug-
gest that different members of the human desmoglein
and desmocollin subfamilies show different patterns of
expression in epidermis (Fig. 3) [2**,15*,16*]. The ma-
jor desmosomal proteins, desmoplakin and plakoglobin
(see below), have not so far revealed different patterns of
expression, but two desmosomal proteins, desmoyokin
and band 6 protein (Table l), are apparently restricted
to stratified epithelia [17,18]. Thus, the protein and gly-
coprotein composition of desmosomesin different loca-
32 Cytoplasm and cell motility

rable 1. Components of desmosomes and hemidesmosomes.

Molecular weight
\lame (X 10-9 Location Comment

hsmosomes

Clycoproteins:
Desmoglein’ 165 tntercellular space and plaque, Three isoforms known
I
possibly to IF attachment LTable 2 and Fig. 2)
Desmocollin I’ 115 Intercellular space and plaque Three isoforms known
Desmocollin II’ 107 I (Table 2 and Fig. 2)
140 kD glycoprotein 140 Intercellular space Minor component
E-cadherin 125 Intercellular space Minor component
22 kD glycoprotein 22 Intercellular space Minor component

Proteins:
Desmoplakin I’ 250 Between plaque and IF Constitutive desmosome
Desmoplakin II* 215 (satellite zone) components. Human
chromosome 6p
Plakoglobin’ a3 Constitutive component
but also in zonula adherens
Desmoyokin’ 680 Plaque circumference Stratified epithelium only
Desmocalmin 240 Plaque Probably bovine
equivalent of
keratocalmin
Keratocalmin ,_ 250 Plaque Probably human
equivalent of desmocalmin
Nuclear lamin 140 Plaque IF-binding activity
B-like protein
Band 6 protein 75 Plaque, between plaque and IF Stratified epithelium
(satellite zone) only
Hemidesmosomes

Clycoproteins:
a6 integrin’ 125 + 30 Transmembrane Human chromosome 2”
(Fig. 2)
p4 integrin’ 195 Transmembrane-cytoplasmic domain Human chromosome 17q llq”
possible extends to IF attachment (Fig. 2)
BPACZ’ 180 Transmembrane Human chromosome
IOq”
Proteins:
HDl’ 500 Inner plaque
BPAGl’ 230 Plaque Human chromosome
6p”
200 kD protein 200 Inner plaque

‘Components referred to in this review. “See [SO-821 for chromosomal locations. IF, intermediate filament.

tions varies. This presumably reflects different adhesive
properties of these junctions and suggests that they play
an important role in epithelial differentiation. Therefore
an immediate challenge is to determine the functional sig-
nificance of these expression patterns.
Cytoplasmic desmosomal proteins:
multigene families
The classification of the major cytoplasmic desmosomal
proteins, desmoplakins and plakoglobin, as members
of multigene protein families has provided further in-
sight into their functions. Plakoglobin, which is present
in adherens junctions as well as desmosomes, forms
a family with j3-catenin and the membrane-associated
Drosopbiln segment polarity gene product, Armadillo,
the last two showing greater homology [ 19,200•,21*].
j3-catenin, also a component of adherens junctions, asso-
members of ciates with the cytoplasmic domain of E-cadherin [21-l.
Plakoglobin (or its homologue) associates both with cad-
herins [20-*,22-l and desmoglein [23], and it is likely
that it may also associate with the larger members of
 Desmosomes and hemidesmosomes Garrod 33

F/YAT
(a)
-COOH II
Desmocollins H,N
COOH I
El E2 E3

Desmoglein COOH

El E2 E3 E4 EA IA

(b) 00

P4 7 7 77 it If

HP cccc COOH

S-S
a6 77 COOH A

HP

COOH I3
%

: Ca?binding sites n Transmembrane domain 0 Fibronectin type Ill repeats

7 N-linked glycosylation sites q Cadherin-like cytoplasmic sequences q a repeats
(7) N-linked glycoslation site in human desmocollins n Desmoglein repeats s-s Disulphide bridge
c Cysteines q Cysteine-rich repeats

Fig. 2. The structure of the major glycoproteins of (a) desmosomes (desmocollins I and II and desmoglein) and (b) hemidesmosomes
(p4 and a6 integrin) as suggested by their deduced amino acid sequences. The transmembrane domains are aligned and the lengths
of the molecules in terms of numbers of amino acids are drawn to scale. Pemphigus vulgaris antigen, a member of the desmoglein
subfamily, has five complete E domains as in desmocollins, only two RUD domains and no DTD domain. Alternatively spliced variants of
desmocollins (I and II), p4 (white boxes over cytoplasmic domain) and a6 (A and 6) integrin are indicated. El-5 are equal-sized extracellular
domains (El-4 are repeats). EA. extracellular anchor domain; IA, intracellular anchor domain; ICS, intracellular cadherin-like segment; IPL,
intracellular proline-rich linker; RUD, repetitive unit domain, DTD, desmoglein terminal domain. Terminology largely after [37**1. Adapted
from Il*l.

ment polarity gene wingless [ 241. This suggests that

Table 2. Desmosomal glycoproteins. the plakoglobin//P-catenin/Armadillo family of proteins
may be involved in morphogenetic signal transduction in
Human Human Human vertebrates. The association of plakoglobin with desmo-
protein Bovine equivalent gene name chromosomal somes suggests that these junctions may have a signalling
assignment function.

Desmoglein Desmoplakins (DPI and DPII) form a multigene family

DC1 Desmoglein (dgl) DSCl 18 of IF-organizing proteins with the 230kD bullous pem-
HDCC - DSC2 18 phigoid antigen (BPAGl), a major cytoplasmic compo-
PVA - DSC3 18 nent of hemidesmosmes, and plectin, a more widely
Desmocollins distributed IF-associated protein. A detailed structural
DGIMII Desmocollins type 2 DSCl 9P comparison of DPI, BPAGl and plectin [25**], made
or type 3 possible by recent availability of sequence [26*-28*,29**]
DGIVIV Probably desmocollin DSC2 18 and rotary shadowing [30,31] data, suggests that these
type 1 proteins form extended dumbbell-shaped dimers with
central coiled-coil rod domains and globular end do-
mains. The carboxyl-terminal globular domains of plectin
the desmocollin subfamily isoforms (i.e. desmocollin I>, and desmoplakins have glycine-rich repeats that are po-
which contain a cytoplasmic cadherin homology region. tential sites for IF interaction. This has been confirmed
The spatial expression of armadillo in Drosophh em- by transfecting COS cells with individual domains of
bryos is regulated by the secreted product of the seg- desmoplaldns; overexpression of the carboxyl-terminal
34 Cytoplasm,and cell motility
Fig. 3. Diagram of epidermis showing regions
desmoglein; PVA, pemphigus vulgaris antigen;
and Table 2 for further details.
domain disrupted keratin filaments, but expression of
the rod domain did not [32**]. Because the carboxyl-
terminal region of desmoplakin interacts with IFS, the
amino-terminal region may bind to cytoplasmic domains
of glycoproteins in the desmosomal plaque, forming a
bridge between the plaque and the IFS (Fig. 1).
Desmosome assembly
Studies of desmosome assembly by MDCK cells have
shown that newly synthesized components appear to
associate only after reaching the cell surface. Before
this, desmoplakin is associated with keratin filaments
and desmoglein, apparently with microtubules
Microtubule-disrupting agents do not, however, inhibit
desmosome assembly [ 34,351, raising doubts about the
role of microtubules in the process. An isolated report
of association between mature desmosomes and micro-
tubules appeared a long time ago [36]. New evidence
shows that the microtubule-associated protein, ~~170,
mediates association between microtubules and desmo-
somes in MDCK cells, and that the junctions may mod-
ulate the properties of microtubules via this interaction
[ 37**]. It is interesting that the amino acid sequence Glu-
Gly-X-Gly-Glu-Glu (where X is any amino acid) is present
in both desmocollins I and II as well as the carboxyl ter-
minus of a-tubulin [9]. This sequence may be involved
in desmosome-microtubule interaction.
In order to study molecular interactions involved in
plaque formation, Franke and colleagues [38**] have
expressed a series of chimeric proteins in cells from
-I DGl, DGIWY
I HDGC, DGII/ m
of maximum expression of desmosomal glycoproteins as indicated in 12**,16*1. DC,
HDCC, human desmoglein from colon; DCII/III and DClViV are desmocollins. See text
A431, a desmosome-forming cervical carcinoma cell line.
These consist of the membrane-spanning domains of the
gap junction protein, connexin 32, and the cytoplasmic
domains of the three major desmosomal gl)roproteins.
The connexin protein is used to target the desmos-
mal cytoplasmic domains to the membrane. Chimeric
constructs with the cytoplasmic domain of the larger
desmocollin variant, desmocollin I, of bovine type 1 or 2,
formed extensive novel gap junction-like structures with
associated desmosome-like plaq~~es containing desmo-
plakin, plakoglobin and attached IF. No such assemblies
were obtained with the chimeric cytoplasmic domain of
the smaller variant desmvcollin II. Chimer+ desmoglein
suprisingly disrupted practically all junction formation
[ 331.
between the transfectecl cells. The results suggest that
desmocollin I cytoplasmic domain contains the ~nolec-
ular signals necessar).for plaque assembl!, (association
with plakogoglobin and desmoplakin ), but leaves uncer-
tainties as to the roles of desmocollin II and desmoglein.
Development and modulation of desmosomal adhesion
Far from being static structures that link cells and IFS,
there is increasing evidence to suggest that the adhesion
of desmosomeschangeswith time ancl can be modulated
in response to signals. %ch modulation is probably im-
portant for cell motility, as well as morphogenesis and
repair of developing and mature tissues.
Assembly of individual mature desmosomesfollowing ini-
tiation of intercellular contact appears to take about 2
hours [39,40]. However, development of desmosomal

adhesion between MDCK cells after contact formation
appears to proceed for at least 24 hours, involving for-
mation of progressively more individual desmosmes of
approximately equal size [41]. Other cell types in viva, as
well as in culture, may take time to develop full desmoso-
mal adhesion. Moreover, the extent of desmosomal adhe-
sion may be affected by external signals; TGF-j3 dramati-
cally increases expression of desmosomes in bronchial
epithelial cells [42*].
After initial assembly, desmosomal adhesion is readily
disrupted by reducing extracellular Ca2+ concentration.
However, with progressive confluent culture, desmosome
Ca2+ -dependence is lost in MDCK cells: the desmo-
somes (but not other junctions) even become resistant
to Ca’+ chelation. Ca’+ independence may well be the
predominant condition of desmosomes in lklo (S Lloyd,
DR Garrod, unpublished data; [43*] >.
Signals can rapidly modulate MDCK desmosomes from a
Ca*+ -independent state to a Cal+-dependent one; first,
wounding the monolayer modulates desmosomes in cells
adjacent to the free edge; second, treatment with the tu-
mour promotor, TPA, modulates desmosomes in all the
cells (S Lloyd, DR Garrod, unpublished data). Although
the significance of such changes is not clear, they may
in some way facilitate disassembly of junctions when
this becomes necessary to permit cell movement. In
addition to modulation during cell locomotion, desmo-
somes have an important role in cell division. However,
in contrast to substratum adhesion, which is altered dur-
ing division, cell-cell contacts are maintained. Epithelial
cells lose neither desmosomal adhesion, nor that of tight
junctions and .zolzt&e aclcet-erztes[44]. Presumably cells
need to maintain contact with their neighbours during di-
vison in order to maintain the integrity of the epithelial
sheet.
How is desmosome assembly regulated in development?
One way would be to regulate the synthesis of one or
more essential desmosomal components. The onset of
assembly of desmosomes between trophectodenn ceils
at the onset of cavitation in the mouse early embryo
may depend upon the initiation of desmosomal glyco-
protein synthesis, and may have importance for initiation
of cavitation and blastocyst formation [45*]. Where cells
are already producing desmosomal components, initia-
tion of contact between them may trigger junction for-
mation. Desmosome formation appears to follow rapidly
on contact formation between medial edge epithelial cells
during palatal fusion in the mouse embryo (C Qiu, MJW
Ferguson, DR Garrod, unpublished data). Once formed,
desmosomes may be modulated during epithelial mor-
phogenesis, for example in kidney tubule development
[46-l.
Hemidesmosomes
A major contribution to the study of hemidesmosomes
was the demonstration that they contain the a6p4 inte-
Desmosomes and hemidesmosomes Garrod 35
grin complex L47-491. a6f34 is by far the most abundant
integrin on the basal surface of epidermal basal cells [48]
and is presumably of major importance in hemidesmo-
somal adhesion to the basement membrane. It may also
play a key role in signal transduction for epidermal strat-
ification/differentiation and basal cell proliferation.
Unlike other p integrins, j34 has an enormous cytoplas-
mic domain (1000 amino acids) containing a series of
fibronectin type III repeats (Fig. 2) [50-521. This is
analagous to the hybrid structure of desmoglein, which
has a cadherin-like extracellular domain for cell-cell ad-
hesion, with a long cytoplasmic domain. Although there
is no sequence homology between desmoglein and p4,
their cytoplasmic domains both clearly represent adap-
tations for membrane-associated plaque formation, and
both may extend beyond the plaques to make direct or
indirect interaction with IFS (Fig. 1).
The cytoplasmic domains of both p4 [50,51] and a6
[53-l show alternatively spliced forms possibly provid-
ing a means of varying ligand alfinity, cytoplasmic inter-
actions or signal transduction. Both the extracellular and
cytoplasmic domains of j34 are subject to tissue-specific
proteolytic processing, and thus have multiple ways of
modulating interactions between the ceil and basement
mem b rdne [ 54==].
There is now substantial evidence that the 180 kD BPAG2
is a type II transmembrane component in hemidesmo-
somes [ 55*,56*]. The carboxyl-terminal region, which
shows homology with collagen, is extracellular, while
the amino-terminal region, which shows homology with
chicken corneal protein, is cytoplasmic [ 55*,57=]. Clearly,
a collagen-related membrane protein could be important
in hemidesmosome-matrix interaction.
What are the ligands for these hemidesmosomal adhe-
sion molecules? Hemidesmosomes interact with thread-
like structures, ‘anchoring filaments’, in the lamina lu-
cida [ 581. A disulphide-bonded heterotrimeric com-
plex, ‘kalinin’, has been identified in anchoring filaments
[59**]. This is identical to the previously identified base-
ment membrane component, BMGOO or ‘nicein’ [GO],
but its relationship to an apparently similar complex,
‘epiligrin’ [6I*], is not yet completely clear (RE Burge-
son, personal communication). Kalinin/nicein has three
subunits of 200, 155 and 14OkD. The 200 and 155 kD
subunits are processed to 165 and 105 kD, respectively,
in culture and tissues, possibly to modulate cell adhesion
[62*].
A newly discovered complex, K-laminin, has the same
distribution in anchoring filament-containing basement
membranes as kalinin [63-m]. This is a type of hy
brid molecule, Y-shaped in rotary shadowing, containing
conventional laminin Bl and B2 chains together with a
19OkD chain related to the 200/165kD chain of kalinin
instead of a conventional laminin A chain (400 kD). As yet
there is no direct evidence that kalinin/nicein, K-laminin
or epiligrin bind to a6p4. Under some circumstances,
or604 binds laminin [64] which, together with merosin, is
36 Cytoplasm and cell motility
present in epidermal basement membrane’[ 65*], but the
positional relationship of these to hemidesmosomes has
not been described. Another potential hemidesmosomal
l&and is 19DEJ-1 [66], but the characterization of this is
not yet clear.
The latest addition to the catalogue of hemidesmosomal
constituents is a 500kD polypeptide, HDl. Located in
the cytoplasmic region, this may be involved in IF as-
sociation [67*]. HI% also occurs in endothelial and glial
cells, which lack hemidesmosomes, where it could be in-
volved in IF-membrane association. The possible role of
BPAGl in hemidesmosome-IF association, as well as its
structural relationship to desmoplakins and plectin are
referred to above. The homology between BPAGl and
desmoplakins represents the only relatedness between
desmosomes and hemidesmosomes so far identified.
Hemidesmosomes, like desmosomes, must be dynamic
structures. When cultures of 804G rat bladder carcinoma
cells are wounded, punctate staining with hemidesmo-
somal antibodies greatly diminishes in cells that enter
wound sites, but returns following wound closure [ 6891.
This reflects modulation of cell-substratum adhesion to
facilitate cell motility. Similar changes might be antici-
pated during wound healing in viva. The major pro-
tein components of hemidesmosomes, again like desmo-
somes, are upregulated by TGF-P treatment [6~], and
hemidesmosomes persist during cell division [ 45=,68*].
Desmosomes, hemidesmosomes and disease
Studies of cell biology and human disease often com-
plement each other. The antigen involved in the au-
toimmune acantholytic blistering disease pemphigus fo-
liaceous has been identified as desmoglein, and the
130kD PVA has now been shown to be a member of
the desmoglein subfamily ([8==]; reviewed in [70]). The
expression patterns of desmoglein and PVA in epider-
mis (Fig. 3) may offer an explanation of appearance of
lesions. Splitting occurs in the upper epidermis in pem-
phigus foliaceous and immediately above the basal layer
in PV. The level of splitting could be related to glycopro-
tein distribution.
Immunoglobulin G purified from PV patient sera on a
P-galactosidase fusion protein containing the two amino-
terminal extracellular domains of PVA causes suprabasil-
lar acantholysis typical of PV when injected into neonatal
mice, but immunoglobulin G aihnity purified against the
three remaining extracellular domains does not [7I**].
However, this is certainly not the whole story, because
the amino-terminal fusion protein could absorb only a
small portion of the pathogenic antibodies from the au-
toimmune serum, suggesting that antibodies to confor-
mational epitopes are also involved.
A recently described disease, paraneoplastic pemphigus,
in which cancer patients display mucocutaneous blister-
ing, involves auto-antibodies to the cytoplasmic proteins
desmoplakins and BPAGl, as well as other uncharacter-
ized epidermal antigens [ 721.
It is difficult to see how auto-antibodies against cytoplas-
mic proteins can play a causative role in autoimmune
disease. Rather, they may arise as a result of ceil damage
and antigen release. It is not clear how the BP antigens
are involved in bullous pemphigoid, although the demon-
stration that BPAG2 is a type II membrane protein seems
to make some kind of direct involvement of antibodies
to the extracellular domain more likely.
An understanding of hemidesmosomal adhesion is cru-
cial to elucidating the aetiology of the junctional form
of epidermolysis bullosa, which is often fatal in early
childhood. Hemidesmosomes are defective in this con-
dition [73], probably because kalinin/nicein is absent or
greatly reduced [74]. Thus the gene for this complex is
a candidate for involvement in the disease.
Desmosomal adhesion is lost in the autosomal domi-
nant acantholytic conditions, Darier’s disease and Hailey-
Hailey disease resulting in cellular internalization of the
desmosomal component [75*,76*]. It seems unlikely that
primary defects in desmosomes are causative, but abnor-
malities in desmosomal genes can now be sought.
The localization of many desmosomal glycoprotein genes
to chromosome 18 [ 11-131 is interesting in view of the
fact that a deletion in 18q is implicated in colorectal can-
cer [2**,77]. However, an extensive study revealed no
gross differences of desmosomal expression in colorectal
carcinoma [44]. Down-regulation of desmoglein expres-
sion was, however, found to correlate with invasion in
transitional cell carcinoma [ 781.
Conclusions and prospects
Epithelia require well developed junctional+oskeletal
networks in order to maintain 1‘ ’ -ctive coverings of
body surfaces. Yet they are highly CI)..;unic structures and
must modulate these networks in order to permit con-
tinued cell renewal and maturation. Both desmosomes
(see above) and hemidesmosomes [79] can assemble
rapidly under appropriate conditions. We are now in a
position to analyze the molecular interactions involved
in that assembly. During maturation of the epidermis
both desmosomes and hemidesmosomes are disassem-
bled, the desmosomes being replaced by junctions with
different but related glycoproteins. Why do they need to
be different? It may be to provide stronger intercellular
adhesion, but adhesion that is still capable of modulation
and replacement. We have very little idea about what sig-
nals regulate these assembly and disassembly processes.
We must also consider that the junctions themselves
transduce signals, perhaps regulating their own assem-
bly or providing information about the state of cellular
differentiation or the degree’of mechanical stress in the
epithelium.
 Desmosomes and hemidesmosomes Garrod 37

Acknowledgements Major Proteins of the Desmosome Junction, Desmogleln

DG (DSG), Desmocollins DGlI7IB (DSC), Desmoplakine
I thank Drs Charles Streuli, Jamie Davies, Jane Collins and Joanne DPI/III (DSP), and Plakoglobin DPIB (JUP). Genomics 1991,
Lorimer, and Kevin Legan and Suzanne Spong for their comments on 10:640-645.
the manuscript. I also thank all those who have generously allowed 12. ARNE~IANN J, SPURR NK, MAGEE Al, BUTON RS: The Human
me access to their manuscripts in press. Gene (DSGJ Coding for HDGC, a Second Member of the
Desmoglein Subfamily of the Desmosomal Cadherins, is,
Lie DSGl Coding for DGI, Assigned to Chromosome 18.
Genomics 1992, 13:484-486.
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(DSG3) Coding for the Pemphigus Vulgaris Antigen is, Like
the Genes Coding for the Two Other Known Desmogleins,
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review, have been highlighted as:
. of special interest 14. PARKERAE, WHEELERGN, ARNE~~ANN J, PIDSLZYSC, A‘~AL~OTS
.. of outstanding interest P, THOMAS CL, REES DA, MAGEE AI, BUXTON RS: Desmo-
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Discusses the structure and molecular composition of desmosome and 15. KING IA. MAGEE AI, REES DA, BLJ~TON RS: Keratinization is
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.. somal and Other Cadherins. Semin CXI Biol1992. 5157-167.
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