| RRC ID |
30720
|
| 著者 |
Emi Y, Harada Y, Sakaguchi M.
|
| タイトル |
Involvement of a di-leucine motif in targeting of ABCC1 to the basolateral plasma membrane of polarized epithelial cells.
|
| ジャーナル |
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.
|
| 巻・号 |
441(1)
|
| ページ |
89-95
|
| 公開日 |
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 Protein 2
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
|
| 引用数 |
3
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
Y79(RBb) cDNA Clones
RBb11B10 (HKR324434). |
