Publication: Lessons from disorders of epidermal
differentiation-associated keratins
Authors
Ishida-Yamamoto, A. ; Takahashi, H. ; lizuka, H.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
A number of diseases have been associated
with mutations in genes encoding keratin intermediate
filaments. Several of these disorders have skin
manifestations, in which histological changes highlight
the role of various different keratins in epidermal
d i fferentiation. For example, mutations in either K1 or
K10 (the major keratin pair expressed in diff e r e n t i a t e d
keratinocytes) usually lead to clumped keratin filaments
and cytolysis. Furthermore, the precise nature of the
mutation has direct implications for disease phenotype.
S p e c i f i c a l l y, mutations in the H1 and alpha-helical rod
domains of K1/K10 result in bullous congenital
ichthyosiform erythroderma, underscoring the critical
role for this keratin filament domain in maintaining
cellular integrity. However, a lysine to isoleucine
substitution in the V1 domain of K1 underlies a form of
palmoplantar keratoderma, which has different cell
biological implications. Keratins are cross-linked into
the cornified cell envelopes through this particular lysine
residue and the consequences of the mutation lead to
changes in keratin-desmosome association and cornified
cell morphology, suggesting a role for this keratin subdomain
in cornified cell envelope formation. Recently,
to extend genotype-phenotype correlation, a frameshift
mutation in the V2 region of the K1 tail domain was
identified in ichthyosis hystrix (Curth-Macklin type), in
which keratin filaments show a characteristic shell-like
structure and fail to form proper bundles. In this case,
the association of desmosomes with loricrin was also
altered, implicating this keratin domain in organizing the
intracellular distribution of loricrin during cornification.
C o l l e c t i v e l y, these mutations in K1/K10 provide a
fascinating insight into both normal and abnormal
processes of epidermal differentiation.
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