Dominant missense mutations in AQP5, encoding the water channel protein Aquaporin 5, underlie diffuse non-epidermolytic palmoplantar keratoderma (NEPPK), a rare skin condition characterized by thickening of the epidermis in palms and soles. Prior to this, AQP5 was only known to be expressed in sweat gland cells in the skin and the role of this water channel in the epidermis remains unclear. To study the role of AQP5 in skin, we have characterized two patient-derived keratinocyte cell lines expressing mutant AQP5Ile45Ser. Phalloidin staining revealed increased levels of actin stress fibres in patient-derived cells compared to control, suggesting an association between AQP5 and the actin cytoskeleton. AQP5Ile45Ser cells also displayed compromised intercellular adhesions, characterized by a significant downregulation of desmosomal proteins at the plasma membrane, and an increased migratory potential, as assessed by an in vitro scratch assay. To gain further insights into the function of AQP5 in keratinocyte biology, we conducted a proximity-dependent labelling screen of physiologically relevant protein-protein interactions, known as BioID, in keratinocytes. Among the potential AQP5 interacting proteins identified, are actin and CD44, a widely expressed cell surface glycoprotein involved in migration and cell adhesion. Proximity ligation assay (PLA) on AQP5Ile45Ser mutant cells versus control revealed a significant increase in the number and fluorescent intensity of PLA signal in mutant keratinocytes, suggesting dysregulated interactions between AQP5Ile45Ser and CD44. These findings indicate that CD44 is a novel AQP5 interacting partner in keratinocytes that may potentially be involved in the regulation of intercellular adhesion, migration and the actin cytoskeleton in the epidermis. AQP5 and CD44 are also both expressed in clear cells of the eccrine sweat gland secretory coil and further understanding of the role of this interaction may give additional insight into the biology of this skin appendage.

ESDR188 - CD44 functions as a novel interacting partner of Aquaporin 5 in keratinocytes

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.