The molecular composition and function of desmosomes

Desmosomes are intercellular adhesive junctions that are particularly prominent in tissues experiencing mechanical stress, such as the heart and epidermis. Whereas the related adherens junction links actin to calcium-dependent adhesion molecules known as classical cadherins, desmosomes link intermediate filaments (IF) to the related subfamily of desmosomal cadherins. By tethering these stress-bearing cytoskeletal filaments to the plasma membrane, desmosomes serve as integrators of the IF cytoskeleton throughout a tissue. Recent evidence suggests that IF attachment in turn strengthens desmosomal adhesion. This collaborative arrangement results in formation of a supracellular network, which is critical for imparting mechanical integrity to tissues. Diseases and animal models targeting desmosomal components highlight the importance of desmosomes in development and tissue integrity, while the downregulation of individual protein components in cancer metastasis and wound healing suggests their importance in cell homeostasis. This chapter will provide an update on desmosome composition, function, and regulation, and will also discuss recent work which raises the possibility that desmosome proteins do more than play a structural role in tissues where they reside.