Journal
AUTOPHAGY
Volume 12, Issue 12, Pages 2500-2501Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1234568
Keywords
autophagosome; INPP5E; Joubert syndrome; lysosome; phosphoinositides
Categories
Funding
- Grants-in-Aid for Scientific Research [25111001] Funding Source: KAKEN
Ask authors/readers for more resources
Macroautophagy (autophagy) is a multistep intracellular degradation system. Autophagosomes form, mature, and ultimately fuse with lysosomes, where their sequestered cargo molecules are digested. In contrast to autophagosome formation, our knowledge of autophagosome-lysosome fusion is limited. In a recent study, we identified a novel regulator of autophagy, INPP5E (inositol polyphosphate-5-phosphatase E), which is essential for autophagosome-lysosome fusion. INPP5E primarily functions in neuronal cells, and knockdown of the corresponding gene causes accumulation of autophagosomes by impairing fusion with lysosomes. Some INPP5E molecules localize at the lysosome, and both lysosomal localization and INPP5E enzymatic activity are crucial for autophagy. In addition, INPP5E decreases PtdIns(3,5)P-2 levels on lysosomes, leading to activation of CTTN (cortactin) and stabilization of actin filaments, which are also essential for autophagosome-lysosome fusion. Mutations in INPP5E are causative for Joubert syndrome, a rare brain abnormality, and our results indicate that defects in autophagy play a critical role in pathogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available