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Ion Channel Reasearch:

Ion channels are integral membrane proteins complexes that allow/control the flow of ions across membranes. In the kidney, the permeability of renal tubules to different solutes and water is determined by a synchronized interplay between an array of epithelial ion channels and transporters at the expense of energy molecules (transcellular). The kidney also utilizes the organelles at cell-cell junctions to transport ions (paracellular). Impairment in these two trans-epithelial ion transport mechanisms lead to a wide range of kidney disorders.

A) Inherited Salt wasting Tubulopathies:

Filtered NaCl is re-absorbed in nephron segments via well co-ordinated interplay of transportation proteins. Identification of transportation processes involving these proteins facilitated the elucidation of rare, recessively inherited salt loosing tubulopathies. Despite various advancements in clinical genetics, a large cohort of the patients with innate salt wasting disorders are genetically inexplicable. Therefore, it is tempting to speculate whether the already known transport systems in the TAL epithelia are described to their actual completeness? The major focus of our research is to understand the complex molecular machinery, dynamics and function of renal Kir channels and their role in renal salt wasting tubulopathies.

B)  Inherited disorders of renal calcium and magnesium handling (FHHNC and HN):

In co-operation with the University of Washington (Prof. Jianghui Hou) we attempt to understand the role of claudins (CLDN) in renal salt handling and decipher the genetic causes of the pathogenesis of Familial Hypercalciuric Hypomagnesemia with Nephrocalcinosis (FHHNC) and Hypercalciuric Nephrolithiasis (HN).

C) Viroporins:

Diverse sets of viruses encode ion channels termed as viroporins, which play an important role in viral infection and viral pathogenicity. In co-operation with the Dept. of Virology, JLU (Prof. John Ziebuhr), we attempt to identify and characterize Corona virus encoded viroporins. The aim of this study is to perform a comprehensive functional characterization of these putative viroporins and identify their cellular and viral interaction partners, as promising novel targets for the development of anti-viral drugs. These studies gained recent importance due to the pandemic distribution of the novel Corona virus SARS-CoV2.

Publikationen

  • Inhalt ausklappen Inhalt einklappen Inherited Salt wasting TubulopathiesInherited Salt wasting Tubulopathies

    1. Schlingmann KP, Renigunta A*, Hoorn EJ, Forst AL, Renigunta V, Atanasov V, Mahendran S, Barakat TS, Gillion V, Godefroid N, Brooks AS, Lugtenberg D, Lake J, Debaix H, Rudin C, Knebelmann B, Tellier S, deBaaij JHF, Weber S, Palygin O, Staruschenko A, Kleta R, Houillier P, Bockenhauer D, Devuyst O, Vargas-Poussou R, Warth R, Zdebik AA, Konrad M. Defects in KCNJ16 cause a novel tubulopathy with hypokalemia, salt wasting, disturbed acid-base homeostasis and sensorineural deafness. JASN (accepted Jan. 2021) (* shared co-first author)

    2. Renigunta A*, Renigunta V, Saritas T, Decher N, Mutig K, Waldegger S. Tamm-Horsfall glycoprotein interacts with renal outer medullary potassium channel ROMK2 and regulates its function. J Biol Chem. 2011;286(3):2224-35. PMID: 21081491 (* Corresponding author)

    3. Renigunta A, Mutig K, Rottermann K, Schlichthörl G, Preisig-Müller R, Daut J, Waldegger S, Renigunta V. The glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and enolase interact with the renal epithelial K+ channel ROMK2 and regulate its function. Cell Physiol Biochem. 2011;28(4):663-72. PMID: 22178878

     4. Peters M, Ermert S, Jeck N, Derst C, Pechmann U, Weber S, Schlingmann KP, Seyberth HW, Waldegger S, Konrad M. Classification and rescue of ROMK mutations underlying hyperprostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int. 2003 Sep;64(3):923-32. PMID: 12911542

  • Inhalt ausklappen Inhalt einklappen Inherited disorders of renal calcium and magnesium handling (FHHNC and HN)Inherited disorders of renal calcium and magnesium handling (FHHNC and HN)

    1. Hou J, Renigunta V, Nie M, Sunq A, Himmerkus N, Quintanova C, Bleich M, Renigunta A, Wolf MTF. Phosphorylated claudin-16 interacts with Trpv5 and regulates transcellular calcium transport in the kidney. Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):19176-19186. PMID: 31488724.

    2. Gong Y, Renigunta V, Zhou Y, Sunq A, Wang J, Yang J, Renigunta A, Baker LA, Hou J. Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization. Mol Biol Cell. 2015 Dec 1;26(24):4333-46. PMID: 26446843.

    3. Gong Y, Renigunta V, Himmerkus N, Zhang J, Renigunta A, Bleich M, Hou J. Claudin-14 regulates renal Ca⁺⁺ transport in response to CaSR signalling via a novel microRNA pathway. EMBO J. 2012 Apr 18;31(8):1999-2012.xPMID: 22373575.

    4. Hou J, Renigunta A, Yang J, Waldegger S. Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18010-5. PMID: 20921420. 

    5. Hou J, Renigunta A, Gomes AS, Hou M, Paul DL, Waldegger S, Goodenough DA. Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium. Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15350-5. PMID: 19706394.

    6. Hou J*, Renigunta A*, Konrad M, Gomes AS, Schneeberger EE, Paul DL, Waldegger S, Goodenough DA. Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Invest. 2008 Feb;118(2):619-28. PMID: 18188451. (*contributed equally)

    7. Konrad M, Hou J, Weber S, Dötsch J, Kari JA, Seeman T, Kuwertz-Bröking E, Peco-Antic A, Tasic V, Dittrich K, Alshaya HO, von Vigier RO, Gallati S, Goodenough DA, Schaller A. CLDN16 genotype predicts renal decline in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol. 2008; 19(1):171-81. PMID: 18003771

    8. Weber S, Schneider L, Peters M, Misselwitz J, Rönnefarth G, Böswald M, Bonzel KE, Seeman T, Suláková T, Kuwertz-Bröking E, Gregoric A, Palcoux JB, Tasic V, Manz F, Schärer K, Seyberth HW, Konrad M. Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol. 2001; 12(9):1872-81. PMID: 11518780.

  • Inhalt ausklappen Inhalt einklappen ViroporinsViroporins

    Grant application is under review