title: Aquaglyceroporins Are the Entry Pathway of Boric Acid in Trypanosoma brucei.
abstract: The boron element possesses a range of different effects on living beings. It is essential to beneficial at low concentrations, but toxic at excessive concentrations. Recently, some boron-based compounds have been identified as promising molecules against Trypanosoma brucei, the causative agent of sleeping sickness. However, until now, the boron metabolism and its access route into the parasite remained elusive. The present study addressed the permeability of T. brucei aquaglyceroporins (TbAQPs) for boric acid, the main natural boron species. To this end, the three TbAQPs were expressed in Saccharomyces cerevisiae and Xenopus laevis oocytes. Our findings in both expression systems showed that all three TbAQPs are permeable for boric acid. Especially TbAQP2 is highly permeable for this compound, displaying one of the highest conductances reported for a solute in these channels. Additionally, T. brucei aquaglyceroporin activities were sensitive to pH. Taken together, these results establish that TbAQPs are channels for boric acid and are highly efficient entry pathways for boron into the parasite. Our findings stress the importance of studying the physiological functions of boron and their derivatives in T. brucei, as well as the pharmacological implications of their uptake by trypanosome aquaglyceroporins.
authors.affiliation: Laboratory of Immunochemistry and Ultrastructure, Institute of Anatomy, Central University of Venezuela, Caracas, Venezuela.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marsiccobetre
authors.affiliation: Laboratory of Immunochemistry and Ultrastructure, Institute of Anatomy, Central University of Venezuela, Caracas, Venezuela.
authors.forename: Alexis
authors.initials: A
authors.lastname: Rodríguez-Acosta
authors.affiliation: Department of Physiology I, University of Tubingen, Tubingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Laboratory of Immunochemistry and Ultrastructure, Institute of Anatomy, Central University of Venezuela, Caracas, Venezuela. Electronic address: kfigarella@gmail.com.
authors.forename: Katherine
authors.initials: K
authors.lastname: Figarella
authors.affiliation: Laboratory of Immunochemistry and Ultrastructure, Institute of Anatomy, Central University of Venezuela, Caracas, Venezuela; Department of Physiology I, University of Tubingen, Tubingen, Germany. Electronic address: nuzcateguia@gmail.com.
authors.forename: Néstor L
authors.initials: NL
authors.lastname: Uzcátegui
mesh_terms: D000818:Animals; D051397:Aquaglyceroporins / Q000378:metabolism*; D001888:Boric Acids / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009865:Oocytes / Q000378:metabolism; D010539:Permeability; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D051397:Aquaglyceroporins; D001888:Boric Acids; C032688:boric acid
keywords: Trypanosoma brucei; aquaglyceroporins; boric acid; heterologous expression