ABCMdb

PMID: 19674157

Ikebuchi Y, Takada T, Ito K, Yoshikado T, Anzai N, Kanai Y, Suzuki H
Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4.
Hepatol Res. 2009 Nov;39(11):1091-107. Epub 2009 Aug 6., [PubMed]

Sentences

No. Mutations Sentence Comment

13 ABCB11 p.Asp482Gly ABCB11 p.Asp482Gly ABCB11 p.Glu297Gly ABCB11 p.Glu297Gly For example, we have found that E297G and D482G mutations in ABCB11, which are frequently found in PFIC2 patients, are associated with the retention of these mutated transporters in the endoplasmic reticulum (ER), although their transport function itself remains normal;20 indeed, following treatment with sodium 4-phenylbutyrate, E297G and D482G mutants appeared on the plasma membrane and were able to excrete substrate bile salts in Madin-Darby canine kidney (MDCK) II cells.21 In addition, insertion of several kinds of mutations in the ABCG5 or ABCG8 gene, which is found in sitosterolemia patients, results in the ER localization of this heterodimer.22 Furthermore, it has been demonstrated that localization of ABCB4 on the bile canalicular membrane is less marked in patients with one of the PFIC3 mutations.15 Concerning the pathogenesis of PFIC3, Dixon et al. tried to examine the localization and function of PFIC3 mutant in HEK293T cells;23 due to the difficulties in establishing a functional assay system of ABCB4 in mammalian cells, they introduced the PFIC3 mutation to the equivalent site of MDR1/ABCB1 to examine the function and localization of the mutated protein.23,24 From this perspective, it is important to identify the mechanism for the cellular localization of membrane transporters. Login to comment