Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic beta cells.
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.
Kambe
Taiho
T
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan. kambe1@kais.kyoto-u.ac.jp
Narita
Hiroshi
H
Yamaguchi-Iwai
Yuko
Y
Hirose
Junko
J
Amano
Tatsuaki
T
Sugiura
Naomi
N
Sasaki
Ryuzo
R
Mori
Koshi
K
Iwanaga
Toshihiko
T
Nagao
Masaya
M
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*
D000911:Antibodies, Monoclonal; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; C457225:SLC30A5 protein, human; C486753:Slc30a5 protein, mouse; D015032:Zinc