A novel variant of mouse MATE-1 H+/organic cation antiporter with a long hydrophobic tail

Kobara, Ayumi; Hiasa, Miki; Matsumoto, Takuya; Otsuka, Masato; Omote, Hiroshi; Moriyama, Yoshinori

doi:10.1016/j.abb.2007.10.010

Cited by 23 publications

(19 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The structure revealed a protein fold consisting of 12 TMHs and supported the view, based on hydropathy analyses of several hundred prokaryotic and plant members of the MATE family, that 12 TMHs make up the functional core of these proteins (12,14). However, hydropathy analysis of the mammalian MATEs consistently identifies 13 TMHs, arising from the presence in these proteins of a very hydrophobic series of residues at the C-terminal end of what, in most other MATE family members, is a long, hydrophilic, C-terminal strand (15). Interestingly, mouse kidney expresses two functional forms of MATE1: "full-length" MATE1 (mMate1b) and an insertion variant (mMate1) that is missing the last 35 C-terminal amino acids (7,15,16).…”

Section: Thmentioning

confidence: 86%

“…However, hydropathy analysis of the mammalian MATEs consistently identifies 13 TMHs, arising from the presence in these proteins of a very hydrophobic series of residues at the C-terminal end of what, in most other MATE family members, is a long, hydrophilic, C-terminal strand (15). Interestingly, mouse kidney expresses two functional forms of MATE1: "full-length" MATE1 (mMate1b) and an insertion variant (mMate1) that is missing the last 35 C-terminal amino acids (7,15,16). We previously showed that the rabbit ortholog of MATE1 has a cytoplasmic N terminus and an extracellular C terminus (17), consistent with an odd number (e.g., 13) of TMHs.…”

Section: Thmentioning

confidence: 99%

See 1 more Smart Citation

Twelve Transmembrane Helices Form the Functional Core of Mammalian MATE1 (Multidrug and Toxin Extruder 1) Protein

Zhang

Xiao

Baker

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: MATE1 (multidrug and toxin extruder 1) mediates renal organic cation secretion. Results: Mammalian MATE1 has 13, not 12, transmembrane helices, but the 13 th TMH is not necessary for transport function. Conclusion: A homology model of MATE1 can use the crystal structure of the prokaryotic MATE protein NorM (12 TMHs). Significance: A MATE1 model is the basis for future structure/activity studies.

show abstract

Section: Thmentioning

confidence: 86%

Section: Thmentioning

confidence: 99%

Twelve Transmembrane Helices Form the Functional Core of Mammalian MATE1 (Multidrug and Toxin Extruder 1) Protein

Zhang

Xiao

Baker

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Furthermore, the K t of relate apical transporters such as mMATE1 and mMATE2 for TEA were reported to be 890 and 710 mM, respectively. 30,31) These later K t values are much higher than that of mOCT2. Taken together, the K t value obtained from mRPT in our study should reflect the function of basolateral organic cation transporters (OCT2) but not apical transporters like MATEs which are the major transporters for organic cation efflux at apical membrane.…”

Section: Fig 1 Effect Of Ovariectomy and Ovariectomy Plus Estrogen mentioning

confidence: 89%

Role of Estrogen in Renal Handling of Organic Cation, Tetraethylammonium: in Vivo and in Vitro Studies

Meetam

Srimaroeng

Soodvilai

et al. 2009

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Urinary excretion of endogenous and exogenous compounds is determined by glomerular filtration and tubular secretion. Secretion of organic cations (OCs), which include endogenous compounds (choline, dopamine), drugs (metformin, cimetidine, cisplatin) and xenobiotics (tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium), is a vectorial transcellular transport process involving uptake of OCs across the basolateral and secretion into urine across the apical side of proximal tubular cells. 1-4)A number of basolateral organic cation transporters (OCTs) have been identified in humans and rodents. [5][6][7][8][9][10] These are at least three subtypes of facilitated OCTs, namely, OCT1 (SLC22A1), OCT2 (SLC22A2), and OCT3 (SLC22A3). Among the OCTs expressed in basolateral membrane, OCT2 is considered as the most important OCT in renal proximal tubule. A decrease in OCT2 expression associated with a decrease in OC secretion has been noted in such pathological conditions as diabetes and chronic renal failure. 11,12) At the apical side, candidates for extrusion of OC via H ϩ /organic cation antiporters include organic cation/ carnitine transporter (OCTN1) 13) and OCTN2. 14) Recently, a multidrug and toxin extrusion (MATE) transporter family was identified as a transporter responsible for the extrusion step.15) Two MATE genes, MATE1 and MATE2, are involved in OC secretion in the kidney. [15][16][17][18] However, little is known about the transport mechanisms and regulation of MATEs.Sex steroid hormones have been implicated in the regulation of renal OC transport. TEA uptake into renal cortical slices and basolateral membrane vesicles of renal proximal tubular cells is higher in male than that of female rat, which correlates with higher mRNA expression level of OCT2, but not of OCT1 or OCT3. 19,20) Testosterone regulates OCT2 function via an androgen receptor-mediated transcriptional pathway.21) Recently, we reported testosterone-stimulated transport of OC in male mice. 22) Estrogen administration produced a small decrease in OCT2 expression level and TEA uptake in male rat and MDCK cells. 20,23) In addition, estrogen reduced OC transport in opossum kidney cell culture via a reduction in OCT1 protein expression. 24) However, there has been no study on the effect of estrogen in vivo, which is important when considering its physiological roles in the whole body. A comprehensive study (molecular, cellular, tissue and intact animal level) of the effects of estrogen on OC transport has received little attention.Therefore, this study was undertaken to determine the role and mechanism of estrogen in the regulation of OC transport in whole animal (mouse) and isolated renal proximal tubules. Studies of gene expression and function of candidate OC transporters were also performed. Our findings showed that estrogen down-regulated OC transport by interfering with OCT2 function at the basolateral membrane. This study examined the effect of estrogen (17b b-estradiol) on renal handling of organic cation, tetraethylammonium (TEA), both in v...

show abstract

“…There are two mouse MATE1 variants, MATE1a and MATE1b (Otsuka et al, 2005;Hiasa et al, 2006;Kobara et al, 2008), consisting of 532 and 567 amino acid residues, respectively. Mammalian MATE transporters commonly possess a long hydrophobic tail at the carboxyl terminal (Otsuka et al, 2005;Ohta et al, 2006;Terada et al, 2006;, but MATE1a is an exception and lacks such a sequence.…”

Section: Mate1 (Slc47a1) Knockout Micementioning

confidence: 99%

“…In mice, OCT1 and OCT2 are expressed in the basolateral membranes of the kidney (Schweifer and Barlow, 1996;Mooslehner and Allen, 1999) and MATE1 is expressed in the brush-border membranes of the kidney (Otsuka et al, 2005;Hiasa et al, 2006;Kobara et al, 2008). In the liver, OCT1 and MATE1 are expressed in the sinusoidal and canalicular membranes, respectively (Schweifer and Barlow, 1996;Green et al, 1999;Otsuka et al, 2005;Hiasa et al, 2006).…”

mentioning

confidence: 99%

Targeted Disruption of the Multidrug and Toxin Extrusion 1 (Mate1) Gene in Mice Reduces Renal Secretion of Metformin

Tsuda

Takato²,

Mizuno³

et al. 2009

Molecular Pharmacology

158

120

View full text Add to dashboard Cite

Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is important for excretion of organic cations in the kidney and liver, where it is located on the luminal side. Although its functional and regulatory characteristics have been clarified, its pharmacokinetic roles in vivo have yet to be elucidated. In the present study, to clarify the relevance of MATE1 in vivo, targeted disruption of the murine Mate1 gene was carried out. The lack of Mate1 expression in the kidney and liver was confirmed by reverse transcription-polymerase chain reaction and Western blot analysis. The mRNA levels of other organic cation transporters such as Octs did not differ significantly between wildtype [Mate1(ϩ/ϩ)] and Mate1 knockout [Mate1(Ϫ/Ϫ)] mice. It is noteworthy that the Mate1(Ϫ/Ϫ) mice were viable and fertile.Pharmacokinetic characterization was carried out using metformin, a typical substrate of MATE1. After a single intravenous administration of metformin (5 mg/kg), a 2-fold increase in the area under the blood concentration-time curve for 60 min (AUC 0 -60 ) of metformin in Mate1(Ϫ/Ϫ) mice was observed. Urinary excretion of metformin for 60 min after the intravenous administration was significantly decreased in Mate1(Ϫ/Ϫ) mice compared with Mate1(ϩ/ϩ) mice. The renal clearance (CL ren ) and renal secretory clearance (CL sec ) of metformin in Mate1(Ϫ/Ϫ) mice were approximately 18 and 14% of those in Mate1(ϩ/ϩ) mice, respectively. This is the first report to demonstrate an essential role of MATE1 in systemic clearance of metformin.

show abstract

A novel variant of mouse MATE-1 H+/organic cation antiporter with a long hydrophobic tail

Cited by 23 publications

References 8 publications

Twelve Transmembrane Helices Form the Functional Core of Mammalian MATE1 (Multidrug and Toxin Extruder 1) Protein

Twelve Transmembrane Helices Form the Functional Core of Mammalian MATE1 (Multidrug and Toxin Extruder 1) Protein

Role of Estrogen in Renal Handling of Organic Cation, Tetraethylammonium: in Vivo and in Vitro Studies

Targeted Disruption of the Multidrug and Toxin Extrusion 1 (Mate1) Gene in Mice Reduces Renal Secretion of Metformin

Contact Info

Product

Resources

About