RRC ID 30720
Author Emi Y, Harada Y, Sakaguchi M.
Title Involvement of a di-leucine motif in targeting of ABCC1 to the basolateral plasma membrane of polarized epithelial cells.
Journal Biochem Biophys Res Commun
Abstract Localization of ATP-binding cassette transporter isoform C1 (ABCC1) to the basolateral membrane of polarized cells is crucial for export of a variety of cellular metabolites; however, the mechanism regulating basolateral targeting of the transporter is poorly understood. Here we describe identification of a basolateral targeting signal in the first cytoplasmic loop domain (CLD1) of human ABCC1. Comparison of the CLD1 amino acid sequences from ABCC1 to ABCC2 revealed that ABCC1 possesses a characteristic sequence, E(295)EVEALI(301), which is comprised of a cluster of acidic glutamate residues followed by a di-leucine motif. This characteristic sequence is highly conserved among vertebrate ABCC1 orthologs and is positioned at a site that is structurally equivalent to the apical targeting signal previously described in ABCC2. Alanine scanning mutagenesis of this sequence in full-length human ABCC1 showed that both L(300) and I(301) residues were required for basolateral targeting of ABCC1 in polarized HepG2 and MDCK cells. Conversely, E(295), E(296), and E(298) residues were not required for basolateral localization of the transporter. Therefore, a di-leucine motif within the CLD1 is a basolateral targeting determinant of ABCC1.
Volume 441(1)
Pages 89-95
Published 2013-11-8
DOI 10.1016/j.bbrc.2013.10.013
PII S0006-291X(13)01673-2
PMID 24129190
MeSH Amino Acid Motifs Amino Acid Sequence Animals Cell Membrane / metabolism* Cell Polarity* Cytoplasm / metabolism Dogs Epithelial Cells / cytology* Epithelial Cells / metabolism* Hep G2 Cells Humans Isoleucine / metabolism Leucine / metabolism* Madin Darby Canine Kidney Cells Molecular Sequence Data Multidrug Resistance-Associated Proteins / chemistry* Multidrug Resistance-Associated Proteins / metabolism* Mutant Proteins / chemistry Mutant Proteins / metabolism Protein Sorting Signals Protein Structure, Tertiary Protein Transport Structure-Activity Relationship Subcellular Fractions / metabolism
IF 2.985
Times Cited 3
DNA material Y79(RBb) cDNA Clones RBb11B10 (HKR324434).