• Bernardo Ortega Ph.D.
  • Assistant Professor
  • email: bortega@brockport.edu
  • Lennon Hall, Room B21, Tel: 395-5190

Our research aims at understanding the mechanisms regulating electrolyte balance. Rare genetic disorders have allowed identification of membrane receptors and transporters implicated in electrolyte reabsorption. Using the mouse as a model, we try to understand the role played by EGF, FGF-23 and their specific receptors in regulating ion channels and transporters known to be involved in kidney transport of potassium and magnesium ions.

Research Description

Research in my lab aims at illuminating the molecular mechanisms involved in the regulation of magnesium reabsorption in the human kidney. Magnesium (Mg2+) is the fourth most abundant mineral in the body and is essential to many physiological processes. Most of the Mg2+ is found in the skeleton or in the intracellular compartment, but approximately 1% of body magnesium is found in blood and can potentially be excreted through the kidneys. Excessive renal Mg2+ excretion may result in hypomagnesemia, a condition often associated with hypertension, poor response to anti-hypertensive medication and cardiac arrhythmias.

Two rare genetic disorders have shown that basolateral inwardly rectifying potassium (BL Kir) channels are critical in driving Mg2+ reabsorption in kidney cells, and have uncovered Epidermal Growth Factor (EGF) as the first known hormone that regulates Mg2+ in the human body. In the distal convoluted tubule (DCT) of kidney nephrons, basolateral Kir channels, combined with the Na, K-ATPase, create the intracellular negative membrane potential required for Mg2+ reabsorption through the apical membrane, explaining the importance of these channels in maintaining adequate Mg2+ balance. It has also been shown that adaptation to a poor Mg2+ diet results in increased serum levels of fibroblast growth factor-23 (FGF-23). Despite these advances, the question of whether any of these factors directly regulates expression or intracellular trafficking of BL Kir channels has never been investigated. To answer this and other important questions regarding the downstream effects of EGF/FGF-23 on specific basolateral transporters, my laboratory uses a combination of biophysical, cell and molecular biology techniques and employes kidney epthelial cell lines and mice as experimental models.

Publications

1. Ortega B, Mason A K, Welling P A. A Tandem Di-Hydrophobic Motif in Kir2.3 mediates AP-2 dependent internalization via direct binding to the alpha sigma 2 subunits. J. Biol. Chem. 287: 26867-75 (2012)
2. Ma D, Taneja T K, Hagen B M, Kim B Y, Ortega B, Lederer W J, Welling P A. Golgi export of the Kir2.1 channel is driven by a trafficking signal located within its tertiary structure. Cell 145: 1102-1115 (2011)
3. Cha S K*, Ortega B*, Kurosu H, Rosenblatt K P, Kuro-o M, Huang C L. Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1. Proc Natl Acad Sci USA. 105: 9805-10 (2008)
4. Ortega B and Welling P A. Molecular Mechanisms of Protein Sorting in Polarized Epithelial Cells. In: Leonard R. Johnson, Fayez K Gishan, Jonathan D Kaunitz, Juanita L Merchant, Hamid M Said and Jackie D Wood. Physiology of the Gastrointestinal Tract. Fifth ed. (1559-82) San Diego, CA; Academic Press. (2012)

Research Pictures

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