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29.10: Desmosomes

JoVE Core
Cell Biology

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29.10: Desmosomes

The term desmosome derives from the Greek words "desmo" and "soma" meaning "adhesion bodies." This structure was first observed during the late 1800s and described as small, dense nodules in the epidermis. Desmosomes are button-like structures that help form an interlinked network of intermediate filaments across the cells. These junctions are  essential to hold cells together under mechanical stress and to maintain tissue integrity. Desmosomes are multi-protein complexes comprising desmosomal cadherins that are linked to intermediate filaments via various adapter proteins.

Desmosomal Cadherins

The cadherins form the extracellular core region of a desmosome and bind cadherins on the adjacent cell. There are two types of cadherins in desmosomes — desmogleins and desmocollins. These transmembrane glycoproteins possess a large extracellular portion comprising four cadherin repeats and one extracellular anchor domain that anchors these proteins to the cell membrane. Heterodimeric pairs of desmogleins and desmocollins form clusters by cis-interactions on the same cell and trans-interactions between adjacent cells. Their cytoplasmic domains can vary in length between the different isoforms due to alternative splicing — for example, there are four desmoglein isoforms and three desmocollin isoforms found in humans.

Adapter Proteins in Desmosomes

The cytoplasmic domains of desmosomal cadherins bind the armadillo family of proteins called plakoglobin and plakophilin, which form a dense plaque. These proteins have the characteristic arm repeats that function as a docking site for different linker proteins, such as desmoplakin. Desmoplakin is the most abundant protein in a desmosomal complex. Their carboxy-terminal contains the plakin repeats, which bind the intermediate filament, thus forming a link between the desmosomal plaque and the cytoskeleton.

Diseases of Desmosome Dysfunction

Desmosomal dysfunction usually manifests as disorders of the heart and skin — tissues typically undergoing high levels of mechanical strain. For example, mutations in the desmoglein genes can cause epidermal thickening and arrhythmogenic right ventricular cardiomyopathy (ARVC). Additionally, autoantibodies targeting the desmosomal cadherins cause the autoimmune disease  pemphigus vulgaris, in which patients exhibit epidermal blisters due to weak cell-cell adhesion.

Suggested Reading


Desmosomes Adhesion Bodies Interlinked Network Intermediate Filaments Tissue Integrity Desmosomal Cadherins Desmogleins Desmocollins Transmembrane Glycoproteins Extracellular Anchor Domain Cis-interactions Trans-interactions Isoforms Alternative Splicing Adapter Proteins

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