On page 555, Nakanishi et al. show that ER stress triggers apoptosis during muscle development. It is the ER stress pathway's first appearance in a nonpathological context.
As muscle precursor cells called myoblasts differentiate, they fuse into multinucleated myotubes. This process is accompanied by a considerable amount of apoptosis—up to 20% of the myoblasts die. The new results show that markers of the ER stress-signaling pathway are up-regulated during this process.
ER stress-induced apoptosis is preceded by the unfolded protein response (UPR), which up-regulates ER chaperones such as BiP. The authors found BiP and ER stress-specific caspase-12 in differentiating myoblasts, including the survivors. In dying myoblasts, death effector caspases such as caspase-9 and -3 were also activated. Survival versus death might depend on the relative amounts of caspases versus antiapoptotic proteins such as XIAPs. Apoptosis might thereby eliminate cells that cannot keep up with...
