Journal
MOLECULAR CELL
Volume 50, Issue 1, Pages 29-42Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2013.01.022
Keywords
-
Categories
Funding
- NIH [CA129536, GM97355, GM74692, GM55692, AG039632, DK62722, CA136754]
- Department of Veterans Affairs Merit Award
Ask authors/readers for more resources
Autophagy is an evolutionarily conserved membrane trafficking process. Induction of autophagy in response to nutrient limitation or cellular stress occurs by similar mechanisms in organisms from yeast to mammals. Unlike yeast, metazoan cells rely more on growth factor signaling for a wide variety of cellular activities including nutrient uptake. How growth factor availability regulates autophagy is poorly understood. Here we show that, upon growth factor limitation, the p110 beta catalytic subunit of the class IA phosphoinositide 3-kinases (PI3Ks) dissociates from growth factor receptor complexes and increases its interaction with the small GTPase Rab5. This p110 beta-Rab5 association maintains Rab5 in its guanosine triphosphate (GTP)-bound state and enhances the Rab5-Vps34 interaction that promotes autophagy. p110 beta mutants that fail to interact with Rab5 are defective in autophagy promotion. Hence, in mammalian cells, p110 beta acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade.
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