The Journal of Cell Biology· 2026Q1
Swollen lysosomes grab Rabs for a CASM-free route to LRRK2 activation
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- Q1SCImago
- 2026year
Short summary
Parkinson's-linked LRRK2 kinase is activated by lysosome swelling, but instead of the typical CASM pathway, it recruits to lysosomes via Rab GTPase binding when PIKfyve is inhibited.
AI-generated from the title and abstract; the full text is not read.
Key points
- Lysosome swelling, caused by PIKfyve inhibition, activates LRRK2 kinase.
- LRRK2 localization to lysosomes occurs via Rab GTPase binding.
- This Rab-mediated recruitment bypasses the previously known CASM pathway.
- The findings highlight an alternative mechanism for LRRK2 activation.
AI-generated from the title and abstract; the full text is not read.
Abstract
Multiple lysosomal stresses activate Parkinson’s-linked LRRK2 kinase, and these involve the so-called “CASM” pathway to help recruit LRRK2 to lysosome surfaces. Clegg et al. (https://doi.org/10.1083/jcb.202511137) show that LRRK2, activated upon lysosome swelling caused by PIKfyve inhibition, instead relies solely on Rab GTPase binding for lysosome localization and activation.
The authors' abstract, as published at the source. The Journal of Cell Biology, 2026 · DOI ↗
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Field: Neurology (Medicine)
NeurologyMedicine