학술논문

LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation
Document Type
article
Source
Journal of Cell Biology. 218(1)
Subject
Underpinning research
2.1 Biological and endogenous factors
Aetiology
1.1 Normal biological development and functioning
Generic health relevance
Actin Cytoskeleton
Actins
Adaptor Proteins
Signal Transducing
Animals
Autophagosomes
Autophagy
Cell Line
Tumor
Gene Expression Regulation
Genes
Reporter
Green Fluorescent Proteins
HEK293 Cells
Humans
Luminescent Proteins
Membrane Proteins
Mice
Microtubule-Associated Proteins
Nuclear Proteins
Osteoblasts
RNA-Binding Proteins
Recombinant Fusion Proteins
Sf9 Cells
Signal Transduction
Spodoptera
Trans-Activators
Biological Sciences
Medical and Health Sciences
Developmental Biology
Language
Abstract
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.