ABCA12 is involved in lipid transport from the Golgi apparatus to cell periphery in epidermal keratinocytes

Mutations in ABCA12 lead to harlequin ichthyosis and lamellar ichthyosis. The keratinocyte lipid transporter ABCA12 is a member of the ATP-binding cassette transporter family, and members of the ABCA subfamily have closely related functions as lipid transporters. Previously, we reported that the pathomechanism of harlequin ichthyosis involves the defective function of the lipid transporter ABCA12.To further elucidate the precise distribution pattern and function of ABCA12, we performed double-labeling immunofl uorescence staining for ABCA12 and for Golgi-associated or lamellar granule-associated molecules both on normal human epidermis and cultured normal human keratinocytes. We studied the precise localization of ABCA12 and other molecules using confocal laser scanning microscope. In normal human epidermis, ABCA12 was observed mainly in the granular layers with glucosylceramide (one of the major lamellar granule contents) and transglutaminase 1 (a cornifi ed cell envelope-associated keratinization marker), but not always colocalized with GM130 and TGN46 (Golgi-related molecules) that were expressed from the lower epidermis. In normal human keratinocytes cultured in high Ca++ concentration medium, ABCA12 colocalized with GM130 (a cis-Golgi- associated molecule), TGN46 (a trans-Golgi-associated molecule) and glucosylceramide. Transglutaminase 1 was restricted to the cell membrane and ABCA12 localization was within the cytoplasm distinct from transglutaminase 1 localization. The present results suggest that ABCA12 is mainly expressed in differentiated, granular layer keratinocytes with glucosylceramide and transglutaminase 1, and, at the subcellular level, ABCA12 is distributed from the cisside of the Golgi apparatus to trans-Golgi network, lamellar granules at the cell periphery. Our results suggest that ABCA12 may play an important role in lipid transport from the cis-side of the Golgi apparatus through the trans-Golgi network, to the cell periphery via lamellar granules in human epidermal granular layer keratinocyte