Cellular trafficking between organelles is typically assured by short motifs that contact carrier proteins to transport them to their destination. Ubiquitin E3 ligase RING finger protein 13 (RNF13), a regulator of proliferation, apoptosis, and protein trafficking, localizes to endolysosomal compartments through the binding of a dileucine motif to clathrin adaptor protein complex AP-3. Mutations within this motif reduce the ability of RNF13 to interact with AP-3. Here, our study shows the discovery of a glutamine-based motif that resembles a tyrosine-based motif within RNF13's C-terminal region that binds to the clathrin adaptor protein complex AP-1, notably without a functional interaction with AP-3. Using biochemical, molecular, and cellular approaches in HeLa cells, our study demonstrates that a RNF13 dileucine variant uses an AP-1-dependent pathway to be exported from the Golgi towards the endosomal compartment. Overall, this study provides mechanistic insights into the alternate route used by variant of RNF13's dileucine sorting motif.
AP-1 contributes to endosomal targeting of ubiquitin ligase RNF13 via a secondary and novel non-canonical binding motif
- Award Group:
- Funder(s): Natural Sciences and Engineering Research Council of Canada
- Award Id(s): RGPIN-2017-05392
- Funder(s):
- Award Group:
- Funder(s): Fonds de recherche du Quebec -- Nature et Technologies
- Funder(s):
- Award Group:
- Funder(s): Centre d'Excellence en Recherche sur les Maladies Orphelines -- Fondation Courtois
- Funder(s):
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- Accepted Manuscript 29 August 2024
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Valérie C. Cabana, Audrey M. Sénécal, Antoine Y. Bouchard, Saïd Kourrich, Laurent Cappadocia, Marc P. Lussier; AP-1 contributes to endosomal targeting of ubiquitin ligase RNF13 via a secondary and novel non-canonical binding motif. J Cell Sci 2024; jcs.262035. doi: https://doi.org/10.1242/jcs.262035
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