Inhibition of TBC1D5 activates Rab7a and can enhance the function of the retromer cargo-selective complex.

ABSTRACT: The retromer complex is a vital component of the endosomal protein sorting machinery 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. Here, we show that inhibition of the GTPase activating protein

SUBMITTER: Seaman MNJ 

PROVIDER: S-EPMC6031384 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature