Dynein motor contributes to stress granule dynamics in primary neurons

Abstract

Mobilization and translation of mRNAs are essential for cellular response to environmental stress, and important to neuronal survive and activity. Studies have shown mRNAs accumulation in stress granules (SGs) in stressed cells. We previously reported the formation of SGs in embryonal carcinoma cells can be regulated by kinases such as focal adhesion kinase (FAK) and RNA binding proteins such as Grb7. However, the formation and disassembly of SGs in neurons remains unclear. In this study, we used arsenite to induce cellular oxidative stress in primary neuronal cultures, and found SGs formation in both cell bodies and neurites of stressed primary spinal cord neurons. By employing siRNA dockdown, we discovered that dynein motor subunit localizes in SG, and is important for SG assembly in neurons. Under stress, dynein motor subunit also facilitates translational repression and enhances the formation and integrity of SG in neurons. By blocking the energy source of dynein motor, both the formation and disassembly of SG are attenuated. These findings demonstrate, for the first time, that dynein motor complex plays a critical role in the formation of neuronal SGs, as well as translation of certain mRNAs. This work was supported by DA11190, DA11806, DK54733, DK60521, K02‐DA13926 to L.‐N. W.