Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis - PubMed
3 hours ago
- #Arl8b
- #Rab11a
- #Lysosome biogenesis
- Arl8b, a small GTP-binding protein, is investigated for its role in lysosome biogenesis, specifically in the trafficking of newly synthesized LAMP1 to lysosomes.
- Using the RUSH assay, it was found that Arl8b localizes to post-endocytic LAMP1-containing vesicles before they fuse with acidic lysosomes.
- Depletion of Arl8b results in Rab11a-dependent recycling of LAMP1 to the plasma membrane, which impairs its delivery to lysosomes.
- Mechanistically, Arl8b recruits the Rab11a GAP, TBC1D9B, to LAMP1-positive membranes, and depletion of TBC1D9B similarly disrupts LAMP1 sorting.
- TBC1D9B knockdown also impairs the retrieval of CI-M6PR from Rab11a- and Rab14-positive endosomes to the trans-Golgi network, affecting pro-cathepsin trafficking and cargo degradation.
- The study reveals that Arl8b-mediated recruitment of TBC1D9B is crucial for inactivating the Rab11a recycling pathway, promoting efficient lysosomal cargo sorting and biogenesis.