Role of the Novel Kinase TNIK on NKCC2 Surface Expression, Phosphorylation and Na Reabsorption in the Thick Ascending Limb

• DOI: 10.1096/fasebj.30.1_supplement.967.12
• Publication Date: 2023-11-26T16:23:51Z
• Authors: Paulo S Caceres; Pablo A Ortiz

NaCl reabsorption by the thick ascending limb (TAL) of loop Henle maintains balance and is important for blood pressure regulation. The apical cotransporter NKCC2 mediates in TAL. In animal models hypertension, phosphorylation at amino‐terminal Thr‐96,101 its trafficking to plasma membrane are enhanced. kinases SPAK OSR1 bind phosphorylate control. addition these, we recently showed that a novel kinase, Traf2 NCK‐interacting kinase (TNIK), also binds phosphorylates NKCC2. However, role TNIK on trafficking, activity regulation unknown. We hypothesized enhances phosphorylation, surface expression NKCC2‐dependent water Na transport. To test this, generated knockout (TNIK −/− ) mice measured isolated TALs. observed was decreased 23 ± 6% (p<0.05) TALs from normal diet. Feeding low‐Na diet increased 179 38% WT mice, but only 56 5% (p<0.05). surface‐to‐intracellular ratio 58 4% 55 16% When placed metabolic cages excreted 99% more urine (WT = 1.03 0.01 ml vs. 2.05 0.13 ml; p<0.05). Baseline excretion similar between strains after 48 hours switching diet, 75% compared 15 0.7 μmol/day 26 5 μmol/day; whether excretion, bumetanide‐induced diuresis natriuresis over six‐hour period following oral administration bumetanide (1.66 mg/g food). On did not observe any difference strains. when 2.66 0.12 2.14 0.11 p<0.05) 239 9 μmol 201 7 μmol; Finally, had lower systolic than fed 123 3.9 mmHg 105 3 mmHg; conclude involved NKCC2‐mediated during adaptation low salt TNIK‐mediated activation may be Support or Funding Information American Heart Association