Bile salt export pump (BSEP/ABCB11): trafficking and sorting disturbances

Curr Mol Pharmacol. 2013 Jul;6(2):95-103. doi: 10.2174/18744672113069990036.

Abstract

Bile salt export pump (BSEP/ABCB11), a member of the family of ATP-binding cassette transporters, is localized on the canalicular membrane of hepatocytes and mediates the efficient biliary excretion of bile acid. The secretion of bile acid into bile by BSEP provides the primary osmotic driving force for bile flow generation. Intrahepatic cholestasis resulting from dysfunction of BSEP can be caused by a mutation in the gene encoding this protein or by acquired factors, such as the side effects of xenobiotics and drugs. In some pathophysiological states, inhibition of BSEP function is associated with its reduced expression on the canalicular membrane caused by impaired trafficking and sorting of BSEP. This fact has generated interest in better understanding the trafficking and sorting mechanism of BSEP. This review describes the molecular characteristics and physiological roles of BSEP, the trafficking and sorting machinery of BSEP, and the mechanisms responsible for disturbance of BSEP, which causes intrahepatic cholestasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / analysis
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Bile Acids and Salts / metabolism*
  • Cholestasis, Intrahepatic / genetics
  • Cholestasis, Intrahepatic / metabolism*
  • Gene Expression Regulation
  • Humans
  • Mutation
  • Protein Transport

Substances

  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters
  • Bile Acids and Salts