Inhibition of TBC1D5 activates Rab7a and can enhance the function of the retromer cargo-selective complex.
Mukadam, Aamir S
Journal of cell science
The Company of Biologists Ltd.
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Seaman, M., Mukadam, A. S., & Breusegem, S. (2018). Inhibition of TBC1D5 activates Rab7a and can enhance the function of the retromer cargo-selective complex.. Journal of cell science, 131 (12)https://doi.org/10.1242/jcs.217398
The retromer complex is a vital component of the endosomal protein sorting machinery being necessary for sorting into both the endosome-to-Golgi retrieval pathway and also the endosome-to-cell-surface recycling pathway. Retromer mediates cargo selection through a trimeric complex comprising VPS35, VPS29 and VPS26 which is recruited to endosomes by binding to Rab7a and Snx3. Retromer function is linked to two distinct neurodegenerative diseases, Parkinson’s disease and Alzheimer’s disease and modulating retromer function has been proposed as an avenue to explore for a putative therapy in these conditions. We hypothesised that activating Rab7a to promote the recruitment of retromer to endosomes could positively modulate its activity and here we show that inhibition of the GTPase activating protein, TBC1D5, can enhance Rab7a activation and lead to a gain-of-function for retromer.
Medical Research Council (MR/L007533/1)
External DOI: https://doi.org/10.1242/jcs.217398
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279303
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/