Digestive Diseases
Bile Acids as Signal Integrators
ATP8B1 and ATP11C: Two Lipid Flippases Important for Hepatocyte FunctionNaik J. · de Waart D.R. · Utsunomiya K. · Duijst S. · Mok K.H. · Oude Elferink R.P.J. · Bosma P.J. · Paulusma C.C.Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands
Keywords: ATP8B1ATP11CPhospholipid flipping |
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Article / Publication Details
Published online: May 27, 2015
Issue release date: May 2015
Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0
ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)
For additional information: https://www.karger.com/DDI
Abstract
P4 ATPases are lipid flippases and transport phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes. Lipid flipping is important for the biogenesis of transport vesicles. Recently it was shown that loss of the P4 ATPases ATP8B1 and ATP11C are associated with severe Cholestatic liver disease. Mutation of ATP8B1 cause progressive familial Intrahepatic Cholestasis type 1 (PFIC1)and benign recurrent intrahepatic cholestasis type 1 (BRIC 1). From our observations we hypothesized that ATP8B1 deficiency causes a phospholipids randomization at the canalicular membrane, which results in extraction of cholesterol due to increase sensitivity of the canalicular membrane. Deficiency of ATP11C causes conjugated hyperbilirubinemia. In our preliminary result we observed accumulation of unconjugated bile salts in Atp11c deficient mice probably because of regulation in the expression or function of OATP1B2. Similar to ATP8B1, ATP11C have regulation on membrane transporters.
© 2015 S. Karger AG, Basel
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References
- Siggs OM, Schnabl B, Webb B, Beutler B: X-linked cholestasis in mouse due to mutations of the P4-ATPase ATP11C. Proc Natl Acad Sci USA 2011;108:7890-7895.
- Siggs OM, et al: The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow. Nat Immunol 2011;12:434-440.
- Yabas M, et al: ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes. Nat Immunol 2011;12:441-449.
- Bull LN, et al: A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 1998;18:219-224.
- Klomp LW, et al: Characterization of mutations in ATP8B1 associated with hereditary cholestasis. Hepatology 2004;40:27-38.
- Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E: Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 2009;4:1.
- Stapelbroek JM, et al: ATP8B1 is essential for maintaining normal hearing. Proc Natl Acad Sci USA 2009;106:9709-9714.
- Pawlikowska L, et al: Differences in presentation and progression between severe FIC1 and BSEP deficiencies. J Hepatol 2010;53:170-178.
- Morotti RA, Suchy FJ, Magid MS: Progressive familial intrahepatic cholestasis (PFIC) type 1, 2, and 3: a review of the liver pathology findings. Semin Liver Dis 2011;31:3-10.
- Bustorff-Silva J, et al: Partial internal biliary diversion through a cholecystojejunocolonic anastomosis - a novel surgical approach for patients with progressive familial intrahepatic cholestasis: a preliminary report. J Pediatr Surg 2007;42:1337-1340.
- Lykavieris P, et al: Progressive familial intrahepatic cholestasis type 1 and extrahepatic features: no catch-up of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation. J Hepatol 2003;39:447-452.
- Paulusma CC, et al: Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport. Hepatology 2006;44:195-204.
- Paulusma CC, Elferink RP, Jansen PL: Progressive familial intrahepatic cholestasis type 1. Semin Liver Dis 2010;30:117-124.
- Pawlikowska L, et al: A mouse genetic model for familial cholestasis caused by ATP8B1 mutations reveals perturbed bile salt homeostasis but no impairment in bile secretion. Hum Mol Genet 2004;13:881-892.
- Eppens EF, et al: FIC1, the protein affected in two forms of hereditary cholestasis, is localized in the cholangiocyte and the canalicular membrane of the hepatocyte. J Hepatol 2001;35:436-443.
- van Mil SW, et al: Fic1 is expressed at apical membranes of different epithelial cells in the digestive tract and is induced in the small intestine during postnatal development of mice. Pediatr Res 2004;56:981-987.
- Cai SY, et al: ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained. Gastroenterology 2009;136:1060-1069.
- Paulusma CC, de Waart DR, Kunne C, Mok KS, Elferink RP: Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem 2009;284:9947-9954.
- Groen A, et al: Abcg5/8 independent biliary cholesterol excretion in Atp8b1-deficient mice. Gastroenterology 2008;134:2091-2100.
- Frankenberg T, et al: The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor. Hepatology 2008;48:1896-1905.
- Chen F, Ellis E, Strom SC, Shneider BL: ATPase class I type 8B member 1 and protein kinase C zeta induce the expression of the canalicular bile salt export pump in human hepatocytes. Pediatr Res 2010;67:183-187.
- Chen F, et al: Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity. Gastroenterology 2004;126:756-764.
- Van der Mark VA, et al: The lipid flippase heterodimer ATP8B1-CDC50A is essential for surface expression of the apical sodium-dependent bile acid transporter (SLC10A2/ASBT) in intestinal Caco-2 cells. Biochim Biophys Acta 2014;1842:2378-2386.
- Van der Velden LM, et al: Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate. Hepatology 2010;51:286-296.
- Sugimoto Y, et al: Failure of parturition in mice lacking the prostaglandin F receptor. Science 1997;277:681-683.
- van de Steeg E, et al: Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs. J Clin Invest 2010;120:2942-2952.
Article / Publication Details
Published online: May 27, 2015
Issue release date: May 2015
Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0
ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)
For additional information: https://www.karger.com/DDI
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