Nutritional restriction leads to protein translation attenuation that results in the storage and degradation of free mRNAs in cytoplasmic assemblies. In this study, we show in Drosophila S2 cells that amino-acid starvation also leads to the inhibition of another major anabolic pathway, the protein transport through the secretory pathway, and to the formation of a novel reversible non-membrane bound stress assembly, the Sec body that incorporates components of the ER exit sites. Sec body formation does not depend on membrane traffic in the early secretory pathway, yet requires both Sec23 and Sec24AB. Sec bodies have liquid droplet-like properties, and they act as a protective reservoir for ERES components to rebuild a functional secretory pathway after re-addition of amino-acids acting as a part of a survival mechanism. Taken together, we propose that the formation of these structures is a novel stress response mechanism to provide cell viability during and after nutrient stress.
Proteins are needed by living cells to perform vital tasks and are made from building blocks called amino-acids. However, if a cell is starved of amino-acids, protein assembly comes to a halt, and if cells are deprived of amino acids for a long time, the cell may die.
To survive short periods of amino-acid starvation, the cell has developed many protective mechanisms. For example, it can start to break down existing proteins, allowing the cell to scavenge and reuse the amino-acids to make other proteins that are more important for short-term survival. The cell may also temporarily halt certain processes: for example, newly constructed proteins may no longer be transported from the cell structure where they are made—called the endoplasmic reticulum—to their final destinations in the cell. However, the protein transport apparatus is also made of proteins and needs to be protected from being broken down so that once starvation ends, the cell can more quickly return to normal working order.
Zacharogianni et al. identify a strategy cells use to store and protect part of their protein transport apparatus during times of stress. Starving fruit fly cells of amino-acids causes the cells to form protective stress assemblies incorporating the proteins associated with the ‘exit sites’ that release proteins from the endoplasmic reticulum. These assemblies are called Sec bodies, and when amino-acid starvation ends, these bodies release the exit site components unharmed. This allows the cell to quickly resume protein transport and so speeds the cell's recovery. If the Sec bodies do not form, the cells are more likely to die during amino-acid starvation.
The Sec bodies are distinct from previously identified stress assemblies that form in the cell during stress, but they share features with them, such as being liquid droplets. Some of these assemblies have been linked to degenerative diseases like amyotrophic lateral sclerosis (ALS). Further research will be necessary to determine if there are any similar harmful side effects associated with the formation of Sec bodies.