Version 1
: Received: 7 August 2024 / Approved: 8 August 2024 / Online: 12 August 2024 (02:51:29 CEST)
How to cite:
Koppin, A.; Chase, L. Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway. Preprints2024, 2024080655. https://doi.org/10.20944/preprints202408.0655.v1
Koppin, A.; Chase, L. Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway. Preprints 2024, 2024080655. https://doi.org/10.20944/preprints202408.0655.v1
Koppin, A.; Chase, L. Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway. Preprints2024, 2024080655. https://doi.org/10.20944/preprints202408.0655.v1
APA Style
Koppin, A., & Chase, L. (2024). Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway. Preprints. https://doi.org/10.20944/preprints202408.0655.v1
Chicago/Turabian Style
Koppin, A. and Leah Chase. 2024 "Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway" Preprints. https://doi.org/10.20944/preprints202408.0655.v1
Abstract
System xc-, the cystine/glutamate exchanger, is a membrane transporter that plays a critical role in the antioxidant response of cells. Recent work has shown that System xc- localizes to the plasma membrane during oxidative stress, allowing for increased activity to support production of glutathione. In this study, we used site-directed mutagenesis to examine the role of C-terminal lysine residues (K422, K472, K473) of xCT (SLC7A11) in regulating System xc-. We observed that K473R exhibits loss of transporter activity and membrane localization and is 7.5 kD lower in molecular weight, suggesting that K473 regulates System xc- trafficking and is modified under basal conditions. After ruling out ubiquitination and neddylation, we demonstrated that unlike WT xCT, K473R lacks N- and O-glycosylation and is sequestered in the endoplasmic reticulum. Next we demonstrated that K473Q, a constitutively acetylated lysine mimic, also exhibits loss of transporter activity, decreased membrane expression, and a 4 kD decrease in molecular weight, however, it is N- and O-glycosylated and localized to the endoplasmic reticulum and Golgi. These results suggest that acetylation and deacetylation of K473 in the endoplasmic reticulum and Golgi, respectively, serves to regulate the progression of the transporter through the biosynthetic pathway.
Keywords
SLC7A11; xCT; System xc-; endoplasmic reticulum acetylation; trafficking; glycosylation
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
