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

Adrien Jezegou, Xavier Leray, Elisa Llinares, Christine Anne, Sylvie Kieffer-Jaquinod, Seana O'Regan, Corinne Sagné, Cecile Debacker, Agnès Journet, Bruno André, et al.

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## ► To cite this version:

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

HAL Id: hal-04652798

https://hal.inrae.fr/hal-04652798v1

Submitted on 18 Jul 2024

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

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UNIVERSITÉ
PARIS DESCARTES

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A. Jézégou¹, X. Leray¹, E. Linares², C. Anne¹, S. Kieffer-Jaquinod³, S. O'Regan¹, C. Sagné¹, C. Debacker¹, A. Journet³, B. André², AA. Zdebick⁴ and B. Gasnier¹

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CYSTINOSIS RESEARCH FOUNDATION

(1) UMR 8192, Université Paris Descartes, Sorbonne Paris Cité / CNRS, Paris, France;
(2) ULB657, Université Libre de Bruxelles, Gosselies, Belgium (3) UMR_S 1038, CEA / Inserm / Université Joseph Fourier, Grenoble, France; (4) University College London, London, England.

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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.

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## 1. PQLC2 localizes to lysosomes

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## 2. Strategy to study PQLC2 mechanism

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## 3. PQLC2 is an electrogenic CAA transporter

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## 4. PQLC2 is pH dependent, yet not coupled to H+ transport

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## 5. PQLC2 is involved in cystinosis treatment

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### A. Cystinosis treatment

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### B. PQLC2 transports the mixed-disulfide (MxD)

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### Future directions:

PQLC2 is driven by lysosomal voltage, not by pH gradient.

* Is PQLC2 regulated by lysosomal ion channels?

* Is CAA transport bidirectional?

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