bioRxiv Science⌕ Search

Biology subjects

Wang, G. M.

Publications and source records attributed to Wang, G. M..

2 recordsLinked to original sources
bioRxiv2024

The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation

The functions of integrins are tightly regulated via multiple mechanisms including trafficking and degradation. Integrins are repeatedly internalized, routed into the endosomal system and either degraded by the lysosome or recycled back to the plasma membrane. The ubiquitin system dictates whether internalized proteins are degraded or recycled. Here, we used a genetic screen and proximity-dependent biotin identification to identify deubiquitinase(s) that control integrin surface levels. We found that a ternary deubiquitinating complex, comprised of USP12 (or the homologous USP46), WDR48 and WDR20, stabilizes {beta}1 integrin (Itgb1) by preventing ESCRT-mediated lysosomal degradation. Mechanistically, the USP12/46-WDR48-WDR20 complex removes ubiquitin from the cytoplasmic tail of internalized Itgb1 in early endosomes, which in turn prevents ESCRT-mediated sorting and Itgb1 degradation.

cell biology↗
bioRxiv2024

Rab7 deficiency induces lysosome formation from recycling endosomes leading to an increased degradation of cell surface proteins

Cell surface receptors such as integrins are repeatedly internalized from and recycled back to the plasma membrane before routed to lysosomes for degradation. In search for modulators of {beta}1 integrin surface stability, we identified the Rab7 small GTPase, believed to be required for lysosome biogenesis, as integrin stabilizer. We show that Rab7 deficiency produces late endosomes and lysosomes with acidic pH, lysosome-specific proteins and membrane architectures that are functional in protein degradation and organelle fusion. Furthermore, Rab7-deficient lysosomes form from Rab4- and transferrin receptor-positive recycling endosomes, resulting in the degradation of proteins designated for recycling. Finally, we also found that overexpression of Rab4 can direct lysosome formation from recycling endosomes in absence as well as presence of Rab7, however, the latter to a much lesser extent. Our findings reveal a lysosome biogenesis and lysosomal protein degradation pathway that becomes dominant in absence of Rab7 or when Rab4 is highly abundant.

cell biology↗