title: Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic beta cells.
abstract: Intracellular homeostasis for zinc is achieved through the coordinate regulation of specific transporters engaged in zinc influx, efflux, and intracellular compartmentalization. We have identified a novel mammalian zinc transporter, zinc transporter 5 (ZnT-5), by virtue of its similarity to ZRC1, a zinc transporter of Saccharomyces cerevisiae, a member of the cation diffusion facilitator family. Human ZnT-5 (hZnT-5) cDNA encodes a 765-amino acid protein with 15 predicted membrane-spanning domains. hZnT-5 was ubiquitously expressed in all tested human tissues and abundantly expressed in the pancreas. In the human pancreas, hZnT-5 was expressed abundantly in insulin-containing beta cells that contain zinc at the highest level in the body. The hZnT-5 immunoreactivity was found to be associated with secretory granules by electron microscopy. The hZnT-5-derived zinc transport activity was detected using the Golgi-enriched vesicles prepared from hZnT-5-induced HeLa/hZnT-5 cells in which exogenous hZnT-5 expression is inducible by the Tet-on gene regulation system. This activity was dependent on time, temperature, and concentration and was saturable. Moreover, zinc at a high concentration (10 mm) inhibited the growth of yeast expressing hZnT-5. These results suggest that ZnT-5 plays an important role for transporting zinc into secretory granules in pancreatic beta cells.
authors.affiliation: Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan. kambe1@kais.kyoto-u.ac.jp
authors.forename: Taiho
authors.initials: T
authors.lastname: Kambe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Narita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamaguchi-Iwai
authors.forename: Junko
authors.initials: J
authors.lastname: Hirose
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Amano
authors.forename: Naomi
authors.initials: N
authors.lastname: Sugiura
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sasaki
authors.forename: Koshi
authors.initials: K
authors.lastname: Mori
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Masaya
authors.initials: M
authors.lastname: Nagao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006367:HeLa Cells; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; C457225:SLC30A5 protein, human; C486753:Slc30a5 protein, mouse; D015032:Zinc