Kidney Week

Abstract: SA-PO1022

Dog and Human Zip10 (SLC39A10) Localization Is More Than Proximal Tubule, Helping to Explain Role in Nephrolithiasis

Session Information

• Fluid and Electrolytes: Basic - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Romero, Michael F., Mayo Clinic College of Medicine, Rochester, Minnesota, United States

Michael F. Romero,

• Holmes, Heather L., Mayo Clinic College of Medicine, Rochester, Minnesota, United States

Heather L. Holmes,

• Landry, Greg M., Massachusetts College of Pharmacy & Health Sciences, Boston, Massachusetts, United States

Greg M. Landry,

• Pandey, Mukesh K., Mayo Clinic College of Medicine, Rochester, Minnesota, United States

Mukesh K. Pandey,

• Jiang, Huailei, Mayo Clinic College of Medicine, Rochester, Minnesota, United States

Huailei Jiang,

• Bansal, Aditya, Mayo Clinic College of Medicine, Rochester, Minnesota, United States

Aditya Bansal,

• Franz, Marie-Christine, CSL Behring AG, Bern, Switzerland

Marie-Christine Franz,

• Montalbetti, Nicolas, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Nicolas Montalbetti,

• Cabrero, Pablo, University of Glasgow, Glasgow, United Kingdom

Pablo Cabrero,

• Dow, Julian A.t., University of Glasgow, Glasgow, United Kingdom

Julian A.t. Dow,

• Furrow, Eva, University of Minnesota, Falcon Heights, Minnesota, United States

Eva Furrow,

Background

In the past several years, we and others have implicated zinc (Zn²⁺) and Zn²⁺ transporters, e.g., SLC39A10 / ZIP10, to have a role in dog and human nephrolithiasis using a Drosophila model. As for other ions and solutes, Zn²⁺ is moved into and out of cells by specific membrane transporters: ZnT, ZIP, and NRAMP/DMT proteins. In rodents, ZIP10 has been localized at the apical membrane of renal proximal tubules (PT), where it is believed to play a role in Zn²⁺ import.

Methods

Our group has used Drosophila as a model of calcium oxalate kidney stones We expressed ZIP10 from dog, human, and Drosophila (CG10006), tested clones for Zn²⁺ uptake, electrogenicity (voltage clamp) and ability to change intracellular pH (pH_i) in Xenopus oocytes. Finally using immunofluorescence, we localized the ZIP10 protein in mouse, dog, human and fly renal structures.

Results

CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. All of these ZIP10-proteins were found to transport ⁶³Zn²⁺ (PET isotope) in oocytes; however, we were unable to elicit membrane currents or pH_i changes with addition of Zn²⁺. The ZIP10 antibody recognizes recombinant and native rodent, dog, human and Drosophila ZIP10 proteins. Immunohistochemistry reveals that Zip10 in higher mammals is found not only in the PT but also in AQP2-positive tubules (collecting duct, CD).

Conclusion

1) CG10006 is the likely ortholog of ZIP10; 2) ZIP10 transport is not electrogenic; 3) ZIP10 transport is not HCO₃^- coupled; 4) ZIP10 in dogs and humans has both PT and CD localization. Together these studies reveal ZIP10 has multiple roles in renal Zn²⁺ transport and may provide additional insights to the role of Zn²⁺ in calcium oxalate nephrolithiasis.

Funding

• NIDDK Support