Biomaterial Database

Bile salt export pump (BSEP/ABCB11): trafficking and sorting disturbances. 2013

Hisamitsu Hayashi, and Yuichi Sugiyama

Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. hayapi@mol.f.u-tokyo.ac.jp

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.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D002780	Cholestasis, Intrahepatic	Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).	Bile Duct Obstruction, Intrahepatic,Biliary Stasis, Intrahepatic,Intrahepatic Cholestasis,Biliary Stases, Intrahepatic,Cholestases, Intrahepatic,Intrahepatic Biliary Stases,Intrahepatic Biliary Stasis,Intrahepatic Cholestases
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074020	ATP Binding Cassette Transporter, Subfamily B, Member 11	ATP-binding cassette, subfamily B, protein (P-glycoproteins) that functions in the ATP-dependent secretion of BILE SALTS into the BILE CANALICULI of HEPATOCYTES. Mutations in the ABCB11 gene are associated with progressive familial intrahepatic cholestasis 2 (see CHOLESTASIS, INTRAHEPATIC).	ABCB11 Protein,ATP Binding Cassette Subfamily B Member 11,ATP Binding Cassette Transporter, Sub-Family B, Member 11,BSEP Protein,Bile Salt Export Pump
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001647	Bile Acids and Salts	Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.	Bile Acid,Bile Salt,Bile Salts,Bile Acids,Acid, Bile,Acids, Bile,Salt, Bile,Salts, Bile
D018528	ATP-Binding Cassette Transporters	A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.	ABC Transporter,ABC Transporters,ATP-Binding Cassette Transporter,ATP Binding Cassette Transporter,ATP Binding Cassette Transporters,Cassette Transporter, ATP-Binding,Transporter, ABC,Transporter, ATP-Binding Cassette,Transporters, ABC,Transporters, ATP-Binding Cassette
D021381	Protein Transport	The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.	Cellular Protein Targeting,Gated Protein Transport,Protein Targeting, Cellular,Protein Translocation,Transmembrane Protein Transport,Vesicular Protein Transport,Protein Localization Processes, Cellular,Protein Sorting,Protein Trafficking,Protein Transport, Gated,Protein Transport, Transmembrane,Protein Transport, Vesicular,Traffickings, Protein