HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chimienti, F. Articles by Seve, M. Search for Related Content PubMed PubMed Citation Articles by Chimienti, F. Articles by Seve, M. Social Bookmarking                What's this?

Identification and Cloning of a ß-Cell–Specific Zinc Transporter, ZnT-8, Localized Into Insulin Secretory Granules

From the Laboratoire des Lésions des Acides Nucléiques, DRFMC/SCIB/LAN, Grenoble, France

SLC30A8, a novel member of the zinc transporter (ZnT) family, was identified by searching the human genomic and expressed sequence tag (EST) databases with the amino acid sequence of all known human ZnT. The protein (369 amino acids) predicted from this gene, ZnT-8, contains six transmembrane domains and a histidine-rich loop between transmembrane domains IV and V, like the other ZnT proteins. We demonstrated by RT-PCR on cDNA libraries and human tissue extracts that the ZnT-8 gene is solely transcribed in the pancreas, mainly in the islets of Langerhans. The gene, named SLC30A8, was cloned and sequenced. Confocal immunofluorescence analysis revealed that a ZnT-8-EGFP (enhanced green fluorescent protein) fusion product colocalized with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Exposure of the ZnT-8-EGFP stably expressing HeLa cells to 75 µmol/l zinc caused an accumulation of zinc in intracellular vesicles compared with cells expressing EGFP alone. These results identified ZnT-8 as a ZnT specific to the pancreas and expressed in ß-cells. Because ZnT-8 facilitates the accumulation of zinc from the cytoplasm into intracellular vesicles, ZnT-8 may be a major component for providing zinc to insulin maturation and/or storage processes in insulin-secreting pancreatic ß-cells.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. S. Kang, M. S. Kim, Y. S. Kim, C. H. Kim, S. J. Han, S. W. Chun, K. Y. Hur, C. M. Nam, C. W. Ahn, B. S. Cha, et al. A Polymorphism in the Zinc Transporter Gene SLC30A8 Confers Resistance Against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients Diabetes, April 1, 2008; 57(4): 1043 - 1047. [Abstract] [Full Text] [PDF]

				J. M. Wenzlau, K. Juhl, L. Yu, O. Moua, S. A. Sarkar, P. Gottlieb, M. Rewers, G. S. Eisenbarth, J. Jensen, H. W. Davidson, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes PNAS, October 23, 2007; 104(43): 17040 - 17045. [Abstract] [Full Text] [PDF]

				L. J. Scott, K. L. Mohlke, L. L. Bonnycastle, C. J. Willer, Y. Li, W. L. Duren, M. R. Erdos, H. M. Stringham, P. S. Chines, A. U. Jackson, et al. A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants Science, June 1, 2007; 316(5829): 1341 - 1345. [Abstract] [Full Text] [PDF]

				Y. Y. Yu, C. P. Kirschke, and L. Huang Immunohistochemical Analysis of ZnT1, 4, 5, 6, and 7 in the Mouse Gastrointestinal Tract J. Histochem. Cytochem., March 1, 2007; 55(3): 223 - 234. [Abstract] [Full Text] [PDF]

				B. Holst, K. L. Egerod, E. Schild, S. P. Vickers, S. Cheetham, L.-O. Gerlach, L. Storjohann, C. E. Stidsen, R. Jones, A. G. Beck-Sickinger, et al. GPR39 Signaling Is Stimulated by Zinc Ions But Not by Obestatin Endocrinology, January 1, 2007; 148(1): 13 - 20. [Abstract] [Full Text] [PDF]

				F. Chimienti, S. Devergnas, F. Pattou, F. Schuit, R. Garcia-Cuenca, B. Vandewalle, J. Kerr-Conte, L. Van Lommel, D. Grunwald, A. Favier, et al. In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion J. Cell Sci., October 15, 2006; 119(20): 4199 - 4206. [Abstract] [Full Text] [PDF]

				R. J. Cousins, J. P. Liuzzi, and L. A. Lichten Mammalian Zinc Transport, Trafficking, and Signals J. Biol. Chem., August 25, 2006; 281(34): 24085 - 24089. [Full Text] [PDF]

				A. V. Gyulkhandanyan, S. C. Lee, G. Bikopoulos, F. Dai, and M. B. Wheeler The Zn2+-transporting Pathways in Pancreatic beta-Cells: A ROLE FOR THE L-TYPE VOLTAGE-GATED Ca2+ CHANNEL J. Biol. Chem., April 7, 2006; 281(14): 9361 - 9372. [Abstract] [Full Text] [PDF]

				T. Suzuki, K. Ishihara, H. Migaki, K. Ishihara, M. Nagao, Y. Yamaguchi-Iwai, and T. Kambe Two Different Zinc Transport Complexes of Cation Diffusion Facilitator Proteins Localized in the Secretory Pathway Operate to Activate Alkaline Phosphatases in Vertebrate Cells J. Biol. Chem., September 2, 2005; 280(35): 30956 - 30962. [Abstract] [Full Text] [PDF]

				T. Suzuki, K. Ishihara, H. Migaki, W. Matsuura, A. Kohda, K. Okumura, M. Nagao, Y. Yamaguchi-Iwai, and T. Kambe Zinc Transporters, ZnT5 and ZnT7, Are Required for the Activation of Alkaline Phosphatases, Zinc-requiring Enzymes That Are Glycosylphosphatidylinositol-anchored to the Cytoplasmic Membrane J. Biol. Chem., January 7, 2005; 280(1): 637 - 643. [Abstract] [Full Text] [PDF]