The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog

Noreen Klein; Nadine Kümmerer; Dominika Hobernik; Dirk Schneider

doi:10.1016/j.fob.2015.07.003

The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog

FEBS Open Bio. 2015 Jul 26:5:640-6. doi: 10.1016/j.fob.2015.07.003. eCollection 2015.

Authors

Noreen Klein¹, Nadine Kümmerer¹, Dominika Hobernik¹, Dirk Schneider¹

Affiliation

¹ Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany.

Abstract

Several point mutations have been identified in human aquaporins, but their effects on the function of the respective aquaporins are mostly enigmatic. We analyzed the impact of the aquaporin 2 mutation V71M, which causes nephrogenic diabetes insipidus in humans, on aquaporin structure and activity, using the bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and structure around the V71M mutation is highly conserved between aquaporin 2 and GlpF. The V71M mutation neither impairs substrate flux nor oligomerization of the aquaglyceroporin. Therefore, the human aquaporin 2 mutant V71M is most likely active, but cellular trafficking is probably impaired.

Keywords: AQP ER, endoplasmic reticulum; AQP, aquaporin; AVP, arginine vasopressin; AVPR2, V2 receptor; Activity; Aquaporin; GlpF; GlpF, glycerol facilitator; GpA, glycophorin A; HM, half-membrane-spanning; NDI, nephrogenic diabetes insipidus; Nephrogenic diabetes insipidus; Protein oligomerization; TM, transmembrane; wt, wild-type.