Meeting report – Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases
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
Pumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey–Hailey, and Grover Disease
Journal of Investigative Dermatology,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 1, 2024
Язык: Английский
Pemphigus vulgaris autoantibodies induce an ER stress response
Journal of Investigative Dermatology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Desmoplakin tail domain position in the desmosomal plaque is isoform dependent
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
Desmosome mutations in keratinocytes fuel melanoma development
Nature Genetics,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 16, 2025
CCDC120 Phase Separation Contributes to Desmosomal Integrity and Cardiac Function
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
The Multi-kinase Inhibitor Midostaurin Mitigates Loss of Intercellular Adhesion and Skin Blistering in Pemphigus Vulgaris
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
The desmosome as a dynamic membrane domain
Current Opinion in Cell Biology,
Год журнала:
2024,
Номер
90, С. 102403 - 102403
Опубликована: Июль 29, 2024
Язык: Английский
Pemphigus vulgaris autoantibodies induce an ER stress response
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