29.10:
Desmosomes
Desmosomes are anchoring junctions found more abundantly in tissues that experience mechanical stress, such as heart muscle and intestinal epithelium.
Cell adhesion at desmosomes is facilitated by desmosomal cadherins, namely desmocollin and desmoglein, which adhere via heterophilic interactions of their extracellular domains.
The cytoplasmic domain of the cadherins binds catenins called plakoglobins and plakophilins, which form a dense plaque on the cytoplasmic side.
The catenins cannot directly bind intermediate filaments, and are linked to them by desmoplakin- a cytoskeletal linker protein belonging to the plakin family.
Desmoplakin's N-terminal domain binds the catenins, and their C-terminal plakin repeats bind the intermediate filaments.
Thus, the desmosome anchors the intermediate filaments of adjacent cells, forming a transcellular cytoskeletal network across the tissue.
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
- Delva, Emmanuella, Dana K. Tucker, and Andrew P. Kowalczyk. "The desmosome." Cold Spring Harbor perspectives in biology 1.2 (2009): a002543.
- Garrod, David, and Martyn Chidgey. "Desmosome structure, composition and function." Biochimica et Biophysica Acta (BBA)-Biomembranes 1778.3 (2008): 572-587.
- Nekrasova, Oxana, and Kathleen J. Green. "Desmosome assembly and dynamics." Trends in cell biology 23.11 (2013): 537-546.