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Regulation of JMY's actin nucleation activity by TTC5/STRAP and LC3 during autophagy
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2018
-
Abstract
- The actin regulator JMY creates filament networks that move membranes during autophagy. Hu and Mullins find that JMY is normally inhibited by interaction with the STRAP protein, but upon starvation, JMY is recruited away from STRAP and activated by LC3.<br />During autophagy, actin filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to actin assembly are poorly understood. We show that, in nonstarved cells, cytoplasmic JMY colocalizes with STRAP, a regulator of JMY’s nuclear functions, on nonmotile vesicles with no associated actin networks. Upon starvation, JMY shifts to motile, LC3-containing membranes that move on actin comet tails. LC3 enhances JMY’s de novo actin nucleation activity via a cryptic actin-binding sequence near JMY’s N terminus, and STRAP inhibits JMY’s ability to nucleate actin and activate the Arp2/3 complex. Cytoplasmic STRAP negatively regulates autophagy. Finally, we use purified proteins to reconstitute LC3- and JMY-dependent actin network formation on membranes and inhibition of network formation by STRAP. We conclude that LC3 and STRAP regulate JMY’s actin assembly activities in trans during autophagy.
- Subjects :
- 0301 basic medicine
Autophagosome
Recombinant Fusion Proteins
Green Fluorescent Proteins
macromolecular substances
Spodoptera
Biology
Actin-Related Protein 2-3 Complex
Article
Mice
03 medical and health sciences
Genes, Reporter
Cell Line, Tumor
Sf9 Cells
Autophagy
Animals
Humans
Molecular Biology
Actin
Research Articles
Adaptor Proteins, Signal Transducing
Actin nucleation
Regulation of gene expression
Osteoblasts
030102 biochemistry & molecular biology
Autophagosomes
Membrane Proteins
RNA-Binding Proteins
Nuclear Proteins
Cell Biology
Actins
Cell biology
Editor’s Corner
Luminescent Proteins
Tetratricopeptide
Actin Cytoskeleton
HEK293 Cells
030104 developmental biology
Gene Expression Regulation
Autophagosome membrane
Trans-Activators
Microtubule-Associated Proteins
Biogenesis
Signal Transduction
Subjects
Details
- ISSN :
- 15548635
- Volume :
- 15
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Autophagy
- Accession number :
- edsair.doi.dedup.....f53948cc83989f205299003c650ac48d