Identification and Characterization of novel KCNJ16 interacting proteins in the pathophysiology of the new complex KCNJ16-associated Hereditary Renal Salt-Wasting Tubulopathy.

• Applicant: Dr. Aparna Renigunta, Ph.D.
• Subject Area: Nephrology ; Anatomy and Physiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 534401031

Enormous efforts in the field of renal physiology have improved our understanding of the tubular transport mechanisms. Despite this progress, a large percentage of renal tubulopathy patients remain genetically inexplicable, suggesting that known transport systems in the tubular epithelia are not described to their actual completeness. This further warrants for studies to fill in the missing links for better diagnosis and eventually better treatment. Our recent study describes a complex disease phenotype comprising a kidney tubulopathy and sensorineural deafness caused by recessive loss of function mutations in KCNJ16. Here, we demonstrate an impaired function of KCNJ16 (Kir5.1) heteromers with KCNJ10 (Kir4.1) and KCNJ15 (Kir4.2). We presume that the effects on two interacting ion channel subunits adds up to a renal phenotype with defective proximal tubular bicarbonate reabsorption and with distal tubular salt wasting. However, the complexity of the phenotype and the differential expression patterns of the subunits point towards involvement of additional ion channel subunits. In the present study, based on our extensive knowledge on potassium channel pathophysiology, we would like to identify novel interacting proteins of KCNJ16 (Kir5.1) and further characterize their interaction and role in renal salt handling.

• DFG Programme: Research Grants