Computational and Mathematical Methods in Medicine / 2015 / Article / Fig 1

Research Article

Evolutionary Influenced Interaction Pattern as Indicator for the Investigation of Natural Variants Causing Nephrogenic Diabetes Insipidus

Figure 1

(a) In normally regulated water absorption in kidney cells, the antidiuretic hormone arginine vasopressin (AVP) is released in the pituitary gland, binds to the V2 receptor (V2R), and subsequently induces a series of phosphorylation reactions which lead to the insertion of aquaporin-2 water channels in the apical membrane that allow water molecules to pass the membrane. (b) Genetic mutations in the gene encoding V2R lead to reduced binding affinity and protein stability in V2R. Dysfunctional V2R mutants cause a significantly reduced amount of inserted aquaporin-2 proteins and thus decrease the water flux through the apical membrane. On the other hand, dysfunctional aquaporin-2 mutants decrease the water reabsorption as well (see (c)). Reduced water reabsorption is directly linked to an increased output of highly diluted urine (polyuria) and excessive drinking (polydipsia) which are the most severe symptoms observable in nephrogenic diabetes insipidus patients [12, 18, 20].

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