RGD Reference Report - Transporters on demand: intrahepatic pools of canalicular ATP binding cassette transporters in rat liver. - Rat Genome Database

RGD Reference Report - Transporters on demand: intrahepatic pools of canalicular ATP binding cassette transporters in rat liver. - Rat Genome Database

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Transporters on demand: intrahepatic pools of canalicular ATP binding cassette transporters in rat liver.
Authors:	Kipp, H Pichetshote, N Arias, I M
Citation:	Kipp H, etal., J Biol Chem. 2001 Mar 9;276(10):7218-24. doi: 10.1074/jbc.M007794200. Epub 2000 Dec 11.
RGD ID:	30309904
Pubmed:	PMID:11113123 (View Abstract at PubMed)
DOI:	DOI:10.1074/jbc.M007794200 (Journal Full-text)
ABC transporter trafficking in rat liver induced by cAMP or taurocholate and [(35)S]methionine metabolic labeling followed by subcellular fractionation were used to identify and characterize intrahepatic pools of ABC transporters. ABC transporter trafficking induced by cAMP or taurocholate is a physiologic response to a temporal demand for increased bile secretion. Administration of cAMP or taurocholate to rats increased amounts of SPGP, MDR1, and MDR2 in the bile canalicular membrane by 3-fold; these effects abated after 6 h and were insensitive to prior treatment of rats with cycloheximide. Half-lives of ABC transporters were 5 days, which suggests cycling of ABC transporters between canalicular membrane and intrahepatic sites before degradation. In vivo [(35)S]methionine labeling of rats followed by immunoprecipitation of (sister of P-glycoprotein) (SPGP) from subcellular liver fractions revealed a steady state distribution after 20 h of SPGP between canalicular membrane and a combined endosomal fraction. After mobilization of transporters from intrahepatic sites with cAMP or taurocholate, a significant increase in the amount of ABC transporters in canalicular membrane vesicles was observed, whereas the decrease in the combined endosomal fraction remained below detection limits in Western blots. This observation is in accordance with relatively large intracellular ABC transporter pools compared with the amount present in the bile canalicular membrane. Furthermore, trafficking of newly synthesized SPGP through intrahepatic sites was accelerated by additional administration of cAMP but not by taurocholate, indicating two distinct intrahepatic pools. Our data indicate that ABC transporters cycle between the bile canaliculus and at least two large intrahepatic ABC transporter pools, one of which is mobilized to the canalicular membrane by cAMP and the other, by taurocholate. In parallel to regulation of other membrane transporters, we propose that the "cAMP-pool" in hepatocytes corresponds to a recycling endosome, whereas recruitment from the "taurocholate-pool" involves a hepatocyte-specific mechanism.

Gene Ontology Annotations Click to see Annotation Detail View

Cellular Component

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
endosome	located_in	IDA		30309904	PMID:11113123	UniProt
intracellular canaliculus	located_in	IDA		30309904	PMID:11113123	UniProt
recycling endosome	located_in	IDA		30309904	PMID:11113123	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Abcb11 (ATP binding cassette subfamily B member 11)

Additional Information