title: Actin nucleation by WH2 domains at the autophagosome.
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.
authors.affiliation: Laboratory of Cancer Biology, Department of Oncology, Medical Sciences Division, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Coutts
authors.affiliation: Laboratory of Cancer Biology, Department of Oncology, Medical Sciences Division, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: La Thangue
mesh_terms: D000199:Actins / Q000378:metabolism*; D020816:Amino Acid Motifs; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D061986:MCF-7 Cells; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000199:Actins; C121977:JMY protein, human; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53