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Bruno Gasnier"Electrophysiological analysis of a lysosomal transporter".

Abstract :

Lysosomal hydrolysis products are exported to the cytosol by H+-driven membrane transporters, a process that is defective in some lysosomal storage diseases including rare neurodegenerative diseases. We used a sorting mutant misrouted to the plasma membrane of Xenopus oocytes to characterize human cystinosin, a lysosomal cystine transporter defective in cystinosis, a predominantly renal disease. Application of cystine at acidic pH elicited an inward current coupled to cystine uptake with a 1:1 charge/cystine ratio. Using voltage dependence analysis of steady state currents as well as transient current recording, we show that cystine binding is coupled to protonation of Asp-305 from the extracellular (lysosomal) compartment, thereby accounting for the H+/cystine symport responsible for cystine efflux from the lysosome.


Selected publications

Molecular and cellular basis of lysosomal transmembrane protein dysfunction.
Ruivo R, Anne C, Sagné C, Gasnier B.
Biochim Biophys Acta. 2009 Apr;1793(4):636-49. Epub 2008 Dec 24.
Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism.
Rutsch F, Gailus S, Miousse IR, Suormala T, Sagné C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Höhne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P.
Nat Genet. 2009 Feb;41(2):234-9. Epub 2009 Jan 11.