Rab7 palmitoylation is required for efficient endosome-to-TGN trafficking

Abstract

Retromer is a multimeric protein complex that mediates endosome-to-TGN and endosome-to-plasma membrane trafficking of integral membrane proteins. Dysfunction of this complex has been linked to Alzheimer's and Parkinson's disease. The recruitment of retromer to endosomes is regulated by Rab7 to coordinate endosome-to- TGN trafficking of cargo-receptor complexes. Rab7 is also required for the degradation of internalized integral membrane proteins such as the epidermal growth factor receptor. We found that Rab7 is palmitoylated and that this modification is not required for membrane anchoring. Palmitoylated Rab7 co-localizes efficiently with and has a higher propensity to interact with retromer than non-palmitoylatable Rab7. Rescue of Rab7 knock out cells by expressing wild-type Rab7 restores efficient endosome-to-TGN trafficking, while rescue with non-palmitoylatable Rab7 does not. Interestingly, Rab7 palmitoylation does not appear to be required for the degradation of epidermal growth factor receptor receptor nor its interaction with its effector RILP. Overall, our results indicate that Rab7 palmitoylation is required for the spatiotemporal recruitment of retromer and efficient endosome-to-TGN Network trafficking of the lysosomal sorting receptors.