Research findings from the group of Prof. Mahak Sharma in collaboration with colleagues from CSIR-IMTECH reveals mechanism of lysosome biogenesis in mammalian cells and shows how cells prevent missorting of lysosomal cargo to the cell surface.
(DOI: https://doi.org/10.1083/jcb.
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Proposed role of Arl8b and its effector, TBC1D9B, in trafficking of the newly synthesized LAMP1 to active lysosomes. Delivery of newly synthesized LAMP1 to active lysosomes follows an indirect trafficking pathway, wherein it exits the TGN in tubular carriers, followed by delivery to the plasma membrane. After endocytosis, LAMP1 is sorted from the AP-3–positive compartment in an Arl8b-dependent manner. Arl8b recruits the Rab11a GAP, TBC1D9B, which inactivates Rab11a to prevent recycling of LAMP1 to the cell surface and facilitates HOPS-mediated fusion of LAMP1-positive vesicles with pre-existing active lysosomes. Upon TBC1D9B depletion, Rab11a levels are increased on the newly synthesized LAMP1 vesicles, leading to recycling of LAMP1 to the cell surface.