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

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