title: Functional characterization of testis-specific rodent multidrug and toxic compound extrusion 2, a class III MATE-type polyspecific H+/organic cation exporter.
abstract: Mammalian multidrug and toxic compound extrusion (MATE) proteins are classified into three subfamilies: classes I, II, and III. We previously showed that two of these families act as polyspecific H(+)-coupled transporters of organic cations (OCs) at final excretion steps in liver and kidney (Otsuka et al. Proc Natl Acad Sci USA 102: 17923-17928, 2005; Omote et al. Trends Pharmacol Sci 27: 587-593, 2006). Rodent MATE2 proteins are class III MATE transporters, the molecular nature, as well as transport properties, of which remain to be characterized. In the present study, we investigated the transport properties and localization of mouse MATE2 (mMATE2). On expression in human embryonic kidney (HEK)-293 cells, mMATE2 localized to the intracellular organelles and plasma membrane. mMATE2 mediated pH-dependent TEA transport with substrate specificity similar to, but distinct from, that of mMATE1, which prefers N-methylnicotinamide and guanidine as substrates. mMATE2 expressed in insect cells was solubilized and reconstituted with bacterial H(+)-ATPase into liposomes. The resultant proteoliposomes exhibited ATP-dependent uptake of TEA that was sensitive to carbonyl cyanide 3-chlorophenylhydrazone but unaffected by valinomycin in the presence of K(+). Immunologic techniques using specific antibodies revealed that mMATE2 was specifically expressed in testicular Leydig cells. Thus mMATE2 appears to act as a polyspecific H(+)/OC exporter in Leydig cells. It is concluded that all classes of mammalian MATE proteins act as polyspecific and electroneutral transporters of organic cations.
authors: Department of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors: Miki
authors: M
authors: Hiasa
authors: Takuya
authors: T
authors: Matsumoto
authors: Toshinori
authors: T
authors: Komatsu
authors: Hiroshi
authors: H
authors: Omote
authors: Yoshinori
authors: Y
authors: Moriyama
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025243:Bacterial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019791:Guanidine / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D019789:Tetraethylammonium / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D017920:Antiporters; D004791:Enzyme Inhibitors; D006835:Hydrazones; C514424:MATE1 protein, mouse; C525124:MATE2 protein, mouse; D027701:Organic Cation Transport Proteins; D011510:Proteolipids; D011994:Recombinant Proteins; C521869:SLC47A1 protein, human; C020485:proteoliposomes; C070053:carbonyl 3-chlorophenylhydrazone; D009536:Niacinamide; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D025243:Bacterial Proton-Translocating ATPases; D019791:Guanidine; C008472:N-methylnicotinamide