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Are desmosomes more than tethers for intermediate filaments?

Abstract

Desmosomes are intercellular adhesive junctions that anchor intermediate filaments at membrane-associated plaques in adjoining cells, thereby forming a three-dimensional supracellular scaffolding that provides tissues with mechanical strength. But desmosomes have also recently been recognized as sensors that respond to environmental and cellular cues by modulating their assembly state and, possibly, their signalling functions.

Key Points

  • Desmosomes are intercellular adhesive junctions that anchor intermediate filaments at membrane-associated plaques in adjoining cells.

  • They are abundant in cells that experience mechanical stress and have a primarily structural function. They associate with distinct sets of intermediate filaments in specific cell types.

  • Desmosomes are now emerging as complex structures with potential to fulfil numerous tissue-specific structural and signalling functions.

  • The components that make up desmosomes can be divided into three superfamilies: desmosomal cadherins, the armadillo family of nuclear and junctional proteins, and plakins. The combinations of protein–protein interactions in which these components engage in a given desmosome are unknown.

  • Models for desmosome structure are based on knowledge of adherens junctions. Although data support the proposed model of cadherin–armadillo–plakin interactions, in reality these may not be strictly linear. Interactions may occur in a more three-dimensional form, for example, with cadherins binding directly to plakins.

  • Desmosomes assemble in response to cell–cell contact and raised levels of extracellular calcium. Sensitivity to calcium levels is lost as desmosomes mature.

  • Adherens junction formation is a prerequisite to desmosome assembly.

  • Desmosomes are sensitive to their environment and respond to growth factors, kinases and phosphatases. Most desmosomal proteins are phosphoproteins, and there are a few cases where phosphorylation has been implicated in regulation of desmosomal protein interactions and therefore desmosome assembly.

  • Desmosomal proteins of the armadillo family may be implicated in signalling during differentiation.

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Figure 1: The junctional complex of epithelial cells.
Figure 2: Schematic structure of principal desmosomal proteins.
Figure 3: Differentiation-specific expression of desmosomal components.
Figure 4: Molecular model of the desmosome.

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Acknowledgements

The authors would like to thank all of our colleagues who provided input and information before publication. Thanks go also to A. Kowalczyk, J. Stanley and members of the Green lab for critical reading of the manuscript, and to T. Mauro for helpful discussion. The authors are supported by grants from the NIH to K.G. and a Warner Lambert Consumer Healthcare Research Fellowship from the Dermatology Foundation to C.G..

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Correspondence to Kathleen J. Green.

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DATABASE LINKS

Desmogleins

Desmocollins

Plakophilin

junctional plakoglobin

desmoplakin

vimentin

keratin

Desmin

plectin

envoplakin

periplakin

α-catenin

β-catenin

Darier's disease

Hailey–Hailey's disease

PKCα

E-cadherin

protein zero

VE-cadherin

EGFR

Src

FGF-1

pemphigus vulgaris

APC

LEF

c-myc

N-cadherin

PKB/AKT

p27

FURTHER INFORMATION

Green lab homepage

Glossary

METAZOANS

Refers to the kingdom Animalia (animals) that comprises roughly 35 phyla of multicellular organisms.

MICROFILAMENT

Cytoskeletal filament typically 6 nm in diameter, consisting of polymerized actin. Microfilaments form the main component of the cellular contractile machinery.

INTERMEDIATE FILAMENT

Cytoskeletal filament, typically 10 nm in diameter, occurring in higher eukaryotic cells.

APICAL MEMBRANE

The surface of an epithelial cell that faces the lumen.

BASOLATERAL MEMBRANE

The surface of an epithelial cell that adjoins underlying tissue.

STRATIFIED EPITHELIAL SHEET

Multilayered epithelial cell sheet.

PEMPHIGUS FOLIACEUS

A rare, blistering autoimmune disease that affects the skin and mucosal membranes.

ENDOCYTOSIS

The uptake of extracellular materials by cells. The plasma membrane invaginates and vesicles pinch off containing endocytosed molecules and plasma membrane components.

HELA CELLS

An established tissue-culture strain of human epidermoid carcinoma cells, containing 70–80 chromosomes per cell. These cells were originally derived from tissue taken from a patient named Henrietta Lacks in 1951.

L CELL FIBROBLASTS

A mouse fibroblast line derived from connective tissue that does not express adhesion molecules.

AXIS DUPLICATION

Duplication of body parts about an axis (for example the anterior–posterior axis) as a result of mutation.

NEURITE

Process extended by a nerve cell that can give rise to an axon or a dendrite.

MESENCHYME

Undifferentiated connective tissue present in the early embryo.

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Green, K., Gaudry, C. Are desmosomes more than tethers for intermediate filaments?. Nat Rev Mol Cell Biol 1, 208–216 (2000). https://doi.org/10.1038/35043032

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