Desmosome assembly and dynamics

Abstract

Desmosomes are intercellular junctions that anchor intermediate filaments to the plasma membrane, forming a supracellular scaffold that provides mechanical resilience to tissues. This anchoring function is accomplished by specialized members of the cadherin family and associated cytoskeletal linking proteins, which together form a highly organized membrane core flanked by mirror image cytoplasmic plaques. Due to the biochemical insolubility of desmosomes, the mechanisms that govern assembly of these components into a functional organelle remained elusive. Recently developed molecular reporters and live cell imaging approaches have provided powerful new tools to monitor this finely-tuned process in real time. Here we discuss studies that are beginning to decipher the machinery and regulation governing desmosome assembly and homeostasis in situ, and how these mechanisms are affected during disease pathogenesis.

Desmosome assembly, homeostasis, and desmosomal disease

“…72 Pkps play a key role in the temporal regulation of these steps. 73 Disruption of desmosomes also occurs in an orderly fashion and in early stages may be induced either artificially by calcium chelation or during certain diseases, such as the autoimmune disease pemphigus. However, after maturation, the dismantling of desmosomes becomes more difficult.…”

“…EGFR expression levels and tyrosine phosphorylation status of the cadherin tails and Pg constitute another mechanism to modulate desmosome assembly and stability. 73 In summary, regulated desmosome remodeling by differential expression and postsynthetic modification of desmosome components is critical for normal epidermal structural integrity, especially that of cell-cell junctions, and epidermal differentiation. Regulation of desmosomal assembly and disassembly, ie, desmosome remodeling, appears to include both inside-out and outside-in signaling mechanisms that cross talk with adherens junctions.…”

150thAnniversary Series: Desmosomes and Autoimmune Disease, Perspective of Dynamic Desmosome Remodeling and Its Impairments in Pemphigus

“…Although desmosomes are mechanically strong adhesive structures between neighboring keratinocytes, they are dynamic units that undergo regular remodeling to allow for keratinocyte outward-migration in the epidermis (Kitajima, 2013;Nekrasova & Green, 2013). This dynamic nature of desmosomes can be well illustrated in experiments using low -high Ca 2 ϩ -switching in culture medium (Hennings et al, 1980;Hennings & Holbrook, 1983;Sato et al, 2000).…”

Desmosomal Cadherins and Signaling: Lessons from Autoimmune Disease

“…After synthesis and posttranslational modifi cation, desmosomal components are transported to the plasma membrane via distinct mechanisms which require differential contributions of the cytoskeleton (Nekrasova & Green, 2013). The integral membrane proteins, Dsgs and Dscs, are translocated to the cell surface via a microtubule-dependent mechanism (Figure 2) (Nekrasova et al, 2011).…”