Zhang et al. (
1.
) demonstrate convincingly that cystinosin has a dual function. In addition to its low-molecular-weight solute transport, it participates in small GTPase-regulated vesicle trafficking and lysosomal localization of LAMP2A, a protein regulating chaperone-mediated autophagy. If cystinosin is absent or impaired, LAMP2A is mislocalized. Such a protein-trafficking function has been suggested previously, based on a bioinformatics analysis (- Zhang J.
- Johnson J.L.
- He J.
- Napolitano G.
- Ramadass M.
- Rocca C.
- Kiosses W.B.
- Bucci C.
- Xin Q.
- Gavathiotis E.
- Cuervo A.M.
- Cherqui S.
- Catz S.D.
Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.
J. Biol. Chem. 2017; 292: 10328-10346
2.
). Cystinosin belongs to a diverse family of homologous proteins named PQ-loop (2.
). Some of the members have been shown to be solute transporters, e.g. plant SWEETs (3.
); others have been shown to be protein cargo receptors in vesicle trafficking, e.g. KDEL receptors (4.
). The molecular functions of many of them, e.g. MPDU1 and CLPT1L, have not yet been found despite their involvement in important biological processes. The cargo-trafficking function has been described for mammalian SWEET1, alias RAG1AP1 (5.
), although not noticed when its solute transport was later discovered (3.
). The most recent discovery of this dual function in cystinosin (1.
) suggests that it could be a general property of many other family members and should always be considered when investigating these important proteins. It could turn out to be particularly relevant for KDEL receptors that show several activities independent of their receptor function (- Zhang J.
- Johnson J.L.
- He J.
- Napolitano G.
- Ramadass M.
- Rocca C.
- Kiosses W.B.
- Bucci C.
- Xin Q.
- Gavathiotis E.
- Cuervo A.M.
- Cherqui S.
- Catz S.D.
Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.
J. Biol. Chem. 2017; 292: 10328-10346
4.
).References
- Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.J. Biol. Chem. 2017; 292: 10328-10346
- Cystinosin, MPDU1, SWEETs, and KDELR belong to a well-defined protein family with putative function of cargo receptors involved in vesicle trafficking.PLoS ONE. 2012; (10.1371/journal.pone.0030876)
- Sugar transporters for intercellular exchange and nutrition of pathogens.Nature. 2010; 468: 527-532
- The KDEL receptor: New functions for an old protein.FEBS Lett. 2009; 583: 3863-3871
- Formation of a physiological complex between TRPV2 and RGA protein promotes cell surface expression of TRPV2.J. Cell Biochem. 2005; 94: 669-683
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Published online: September 08, 2017
Edited by Thomas SöllnerFootnotes
The author declares that he has no conflicts of interest with the contents of this article.
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© 2017 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
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