title: Adenosine triphosphate binding cassette (ABC) transporters are expressed and regulated during terminal keratinocyte differentiation: a potential role for ABCA7 in epidermal lipid reorganization.
abstract: Central aspects of the cellular lipid trafficking mechanisms that occur during keratinocyte differentiation are still not well understood. In the past years, evidence has accumulated to suggest that members of the superfamily of adenosine triphosphate binding cassette (ABC) transporters are critically involved in the transmembrane transport of cellular lipids. To test the hypothesis that ABC molecules are potentially involved in the epidermal transport of sphingolipids, glycerophospholipids, cholesterol, and fatty acids, we performed mRNA expression profiling of all currently known ABC molecules during in vitro differentiation of human keratinocytes and HaCaT cells. We identified six ABC molecules that displayed significant regulation during differentiation of these cells. The recently cloned transporter ABCA7 was highly expressed in keratinocytes and HaCaT cells and upregulated during differentiation. Overexpression of ABCA7 in HeLa cells resulted in increased expression of intracellular and cell surface ceramide and elevated intracellular phosphatidylserine levels. Given the observation that during terminal keratinocyte differentiation intracellular and surface ceramide levels are increased, our results render ABCA7 a candidate regulator of ceramide transport in this process. In addition to ABCA7, the cholesterol transporters ABCB1 and ABCG1 and the glutathione/glucuronide sulfate transporters ABCC1, ABCC3, and ABCC4, were strongly upregulated during keratinocyte and HaCaT cell differentiation. These findings support the notion that ABCB1 and ABCG1 are potentially implicated in cholesterol transport, whereas ABCC1, ABCC3, and ABCC4 are candidate regulators of the translocation of sulfated lipids during stratum corneum keratinization. Our results suggest specific biologic functions for members of the ABC transporter family in epidermal lipid reorganization during terminal keratinocyte differentiation.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
authors.forename: Danuta
authors.initials: D
authors.lastname: Kielar
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Kaminski
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.forename: Armin
authors.initials: A
authors.lastname: Piehler
authors.forename: Jürgen J
authors.initials: JJ
authors.lastname: Wenzel
authors.forename: Christoph
authors.initials: C
authors.lastname: Möhle
authors.forename: Susanne
authors.initials: S
authors.lastname: Heimerl
authors.forename: Thomas
authors.initials: T
authors.lastname: Langmann
authors.forename: Sven O
authors.initials: SO
authors.lastname: Friedrich
authors.forename: Alfred
authors.initials: A
authors.lastname: Böttcher
authors.forename: Stefan
authors.initials: S
authors.lastname: Barlage
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Drobnik
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002518:Ceramides / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D008938:Mitosis / Q000502:physiology; D010718:Phosphatidylserines / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
chemical_list: C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters; D002518:Ceramides; D010718:Phosphatidylserines; D012333:RNA, Messenger