title: The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog.
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.
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany.
authors.forename: Noreen
authors.initials: N
authors.lastname: Klein
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kümmerer
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany.
authors.forename: Dominika
authors.initials: D
authors.lastname: Hobernik
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schneider
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