Rxivist logo

LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes

By Luis Bonet-Ponce, Alexandra Beilina, Chad D. Williamson, Eric Lindberg, Jillian H Kluss, Sara Saez-Atienzar, Natalie Landeck, Ravindran Kumaran, Adamantios Mamais, Christopher K. E. Bleck, Yan Li, Mark R. Cookson

Posted 24 Jan 2020
bioRxiv DOI: 10.1101/2020.01.23.917252 (published DOI: 10.1126/sciadv.abb2454)

Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are a cause of familial and sporadic Parkinson disease (PD). Nonetheless, the biological functions of LRRK2 remain incompletely understood. Here, we observed that LRRK2 is recruited to lysosomes that have a ruptured membrane. Using unbiased proteomics, we observed that LRRK2 is able to recruit the motor adaptor protein JIP4 to permeabilized lysosomes in a kinase-dependent manner through the phosphorylation of RAB35 and RAB10. Super-resolution live cell imaging microscopy and FIB-SEM revealed that once at the lysosomal membrane, JIP4 promotes the formation of LAMP1-negative lysosomal tubules that release membranous content from ruptured lysosomes. Released vesicular structures are able to interact with other lysosomes. Thus, we described a new process that uses lysosomal tubulation to release vesicular structures from permeabilized lysosomes. LRRK2 orchestrates this process that we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2) that, given the central role of the lysosome in PD, is likely to be disease relevant.

Download data

  • Downloaded 2,031 times
  • Download rankings, all-time:
    • Site-wide: 8,362
    • In cell biology: 185
  • Year to date:
    • Site-wide: 53,178
  • Since beginning of last month:
    • Site-wide: 58,593

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide