title: ABCC6 is a basolateral plasma membrane protein.
abstract: BACKGROUND
  ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein.
  
  
  OBJECTIVE
  In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment.
  
  
  RESULTS
  We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum.
  
  
  CONCLUSIONS
  Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation.
authors.affiliation: Institute of Enzymology, RCNS, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Viola
authors.initials: V
authors.lastname: Pomozi
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Saux
authors.forename: Christopher
authors.initials: C
authors.lastname: Brampton
authors.forename: Ailea
authors.initials: A
authors.lastname: Apana
authors.forename: Attila
authors.initials: A
authors.lastname: Iliás
authors.forename: Flóra
authors.initials: F
authors.lastname: Szeri
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Katalin
authors.initials: K
authors.lastname: Monostory
authors.forename: Sándor
authors.initials: S
authors.lastname: Paku
authors.forename: Balázs
authors.initials: B
authors.lastname: Sarkadi
authors.forename: Gergely
authors.initials: G
authors.lastname: Szakács
authors.forename: András
authors.initials: A
authors.lastname: Váradi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000254:Sodium-Potassium-Exchanging ATPase; C102029:ABCC6 protein, human; C504743:Abcc6 protein, mouse
keywords: arterial calcification, generalized, of infancy; hepatocytes; pseudoxanthoma elasticum; soft tissue calcification