Identification and characterization of a new cationic amino acid transporter named PQ-Loop-Containing protein 2 (PQLC2)

Adrien Jezegou (1) , Xavier Leray (1) , Elisa Llinares (2) , Christine Anne (1) , Sylvie Kieffer-Jaquinod (3) , Seana O'Regan (1) , Corinne Sagné (1) , Cecile Debacker (1) , Agnès Journet (4) , Bruno André (2) , Anselm A Zdebik (5) , Bruno Gasnier (1)

1 UMR 8192 - Laboratoire de dynamique membranaire et maladies neurologiques
2 ULB - Université libre de Bruxelles
3 BGE - UMR S1038 - Laboratoire de Biologie à Grande Échelle
4 GenChem - Genetics and Chemogenomics
5 UCL - University College of London [London]

Cystinosin, the lysosomal cystine exporter defective in cystinosis, is the founding member of a 7-TM membrane protein family related to bacteriorhodopsin and characterized by a duplicated motif termed PQ loop. The molecular function of the other PQ-loop proteins remains unknown. Recently, we used proteomics, yeast genetic and transport studies to characterize PQLC2, a new lysosomal cationic amino acid (CAA) transporter (Jezegou et al., PNAS 2012). Here, we present some aspects of this work and give new elements concerning its biophysical mechanism. This study also brings new insights concerning the molecular mechanism by which cysteamine acts in cystinosis treatment. It shows also that PQLC2, despite its pH sensitivity, is not coupled to proton transport. This feature support that PQLC2 activity is very sensitive to lysosomal voltage.

Domaines: Sciences du Vivant [q-bio]

Adrien Jezegou, Xavier Leray, Elisa Llinares, Christine Anne, Sylvie Kieffer-Jaquinod, et al.. Identification and characterization of a new cationic amino acid transporter named PQ-Loop-Containing protein 2 (PQLC2). 19th European Study Group on Lysosomal Diseases (ESGLD) Workshop, Sep 2013, Seggau castle, Austria. ⟨hal-04652798⟩