Three signaling pathways essential for Sec body formation

Cells contain many compartments, each of which has a specialized function. One of these compartments is the endoplasmic reticulum (ER), which plays an important role in the production and transport of proteins destined to be secreted to the transmembrane and extracellular medium. These proteins exit the location where they were produced through so-called exit sites. One of the key proteins of the ER exit sites’ function and organization is Sec16.

Sec body formation

When cells are under stress – for example when they are starved of amino acids, the building blocks of proteins – the exit sites of the ER are remodeled. In particular, Sec16 coalesces together with other components into large stress assemblies called Sec bodies. The Sec bodies are essential for cell survival during stress and dissolve once the stress is relieved.

Cell starvation

In a new paper published in the Journal of Cell Science, researchers from the group of Catherine Rabouille demonstrate that three signaling pathways need to be activated to lead to Sec body formation in the cells of the fruit fly (Drosophila). First, the absence of amino acids makes the cells more sensitive to salt, which creates stress and activates SIK kinases – enzymes that are involved in controlling chemical reactions within cells. When the salt stress is high, the activation of SIK kinases alone is sufficient to lead to Sec body formation.

Reinforcement

Furthermore, the absence of amino-acids also activates PERK and IRE1, two kinases that are at the core of ER stress. The activation of these kinases needs to be combined with a moderate level of salt stress to induce the formation of Sec bodies. Additionally, SIK, PERK and IRE1 seem to reinforce each other through the stimulation of the “Unfolded Protein Response”, which plays a key role in Sec body formation.

Future steps

Cells are constantly subjected to stress. Therefore, chemical and cellular mechanisms are place to help them survive during stress and thrive upon stress relief. One of these mechanisms is Sec body formation. Although their new paper provides more insight into the activation of this mechanism, the researchers from the Rabouille group also still have some challenges ahead: to identify the other components of the Sec bodies, as well as to show that it is a process conserved in evolution.

Publication