Disease relevance of Atp8b1

• These results demonstrate the key role of Atp8b1 in bile salt homeostasis and highlight the importance of bile salt hydroxylation in the prevention of cholestasis [1].
• The mouse phenotype reveals that loss of Atp8b1 disrupts bile salt homeostasis without impairment of canalicular bile secretion; in humans this process is likely to be obscured by early onset of severe liver disease [1].
• Mutations in the FIC1 gene constitute the molecular defect in familial intrahepatic cholestasis I (Fic1 [Byler's disease]) and benign recurrent intrahepatic cholestasis [2].

High impact information on Atp8b1

• In the small intestine, Fic1 was localized to the apical membrane of epithelial cells [2].
• The distribution of Fic1 in liver plasma membrane fractions from control and taurocholate-treated rats correlated positively with adenosine triphosphate (ATP)-dependent aminophospholipid (phosphatidyl-serine) translocase activity [2].
• This report describes the localization of Fic1 in rat liver and intestine, as well as biochemical and transfection studies that support its function as an energy-dependent aminophospholipid translocase [2].
• The 11 sequenced V lambda I proteins used in this study were assigned to sub-subgroups by comparison with the previously published germ-line V lambda Ia, V lambda Ib, and V lambda Ic sequences [3].
• Through the use of a functionally unbiased signal peptide trap screen, we have discovered an ATP-dependent aminophospholipid transporter that is exclusively expressed in the acrosomal region of spermatozoa; it is about 62% similar to the flippase, FIC1 [4].

Anatomical context of Atp8b1

• These studies indicate that FIC1 is a canalicular P-type ATPase that participates in maintaining the distribution of aminophospholipids between the inner and outer leaflets of the plasma membrane [2].
• In conclusion, these data show that Fic1 is expressed in a tissue-specific and developmentally regulated fashion at the apical membranes of epithelial cells [5].
• Immunoblot and RT-PCR analysis indicated Fic1 is expressed abundantly in regions of the adult gastrointestinal tract of humans and mice [5].
• Immunohistochemistry revealed that Fic1 was localized to the apical membranes of enterocytes, pancreatic acinar cells, gastric pit epithelial cells, and hepatocytes and cholangiocytes [5].
• FIC1, the protein affected in two forms of hereditary cholestasis, is localized in the cholangiocyte and the canalicular membrane of the hepatocyte [6].

Associations of Atp8b1 with chemical compounds

• Transient transfection of CHOK1 cells with FIC1 cDNA resulted in appearance of FIC1 in membrane preparations and energy-dependent PS translocation in cells [2].

Other interactions of Atp8b1

• ATP8B1 encodes FIC1, which is expressed in several tissues, most prominently in the intestine, pancreas, and stomach and, to a much lesser extent, in the liver [5].

Analytical, diagnostic and therapeutic context of Atp8b1

• Immunocytochemistry of rat liver and immunoblotting of membrane fractions localized Fic1 to the canalicular, but not basolateral, plasma membrane domain [2].
• Double label immunofluorescence of murine liver revealed that FIC1 colocalized with cytokeratin 7 in cholangiocytes [6].

References