Figure 1. Keratotic papules in Darier's disease.
Figure 2. Skin fragility and painful erosions dominate the clinical picture in some patients with Darier's disease.
Figure 3. Skin biopsy from Darier's disease reveals a characteristic dyskeratosis with suprabasal acantholysis secondary to breakdown of the desmosome adhesion junctions. The epidermis shows hyperproliferative budding beneath the dyskeratotic plug.
Figure 4. Painful erosions in the flexures characterize Hailey-Hailey disease. The skin is more fragile than in Darier's disease. Flexural skin may become rather thickened and papillomatous, but patients do not develop the hyperkeratotic papules that are seen in Darier's disease.
Figure 5. Diagram showing the predicted secondary structure of SERCA2. The 10 transmembrane helices anchoring the molecule to the endoplasmic reticulum (ER) membrane are linked by stalk helices to a cytoplasmic headpiece with the ß-strand, phosphorylation and nucleotide binding domains. Both the N- and C-terminal segments of SERCA2a are exposed on the cytoplasmic surface of the ER membrane whereas in SERCA2b an extended tail section enters the lumen of the ER. The active site for ATP hydrolysis is formed in the phosphorylation and nucleotide binding domains. The transmembrane domain containing Ca2+ binding sites forms the channel for transport of Ca2+ into the ER.
Figure 6. Simplified view of a keratinocyte showing the localization of SERCA2 and SPCA1. Proteins synthesized in association with the endoplasmic reticulum membrane are transported to the Golgi apparatus for further processing before being targeted to various destinations. The Golgi apparatus consists of flattened cisternae with two distinct faces. Proteins enter at the cis face close to the endoplasmic reticulum but exit from the trans face. SERCA2 is found in association with the endoplasmic reticulum membrane, while SPCA1 is found linked to the Golgi apparatus, where it seems to be associated primarily with the membranes of the trans or exit face.