Abstract
Autophagy is a catabolic process whereby cytosolic components and organelles are degraded to recycle key cellular materials. It is a constitutive process required for proper tissue homoeostasis but can be rapidly regulated by a variety of stimuli (for example, nutrient starvation and chemotherapeutic agents). JMY is a DNA damage-responsive p53 cofactor and actin nucleator important for cell survival and motility. Here we show that JMY regulates autophagy through its actin nucleation activity. JMY contains an LC3-interacting region, which is necessary to target JMY to the autophagosome where it enhances the autophagy maturation process. In autophagosomes, the integrity of the WH2 domains allows JMY to promote actin nucleation, which is required for efficient autophagosome formation. Thus our results establish a direct role for actin nucleation mediated by WH2 domain proteins that reside at the autophagosome.
Highlights
Autophagy is a catabolic process whereby cytosolic components and organelles are degraded to recycle key cellular materials
The LC3-interacting region (LIR) in JMY is required for actin nucleation activity, which is necessary for autophagosome formation and maturation
As nuclear JMY is responsive to a variety of cellular stressors such as UV and hypoxia[10,12,14], and is resident in the cytoplasm where it can influence actin nucleation, we were interested in examining whether JMY takes on a more general role in cellular stress, such as autophagy
Summary
Autophagy is a catabolic process whereby cytosolic components and organelles are degraded to recycle key cellular materials It is a constitutive process required for proper tissue homoeostasis but can be rapidly regulated by a variety of stimuli (for example, nutrient starvation and chemotherapeutic agents). We found that JMY is recruited to LC3-containing autophagosomes when cells are exposed to a variety of autophagy-inducing agents, including starvation and drug treatment. This requires the amino (N)-terminal region of JMY, which contains an LC3-interacting region (LIR), required for JMY to localize at the autophagosome where it enhances autophagosome formation and maturation. Our results establish for the first time actin nucleation at the autophagosome and suggest a mechanistic role for actin in autophagosome formation and maturation
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