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Microtubule dependency of stress granule dynamics

Stress granule formation is an important mechanism for cell survival during stress that remains largely uncharacterized. We studied the role of microtubules in the formation, maintenance, and disassembly of stress granules. During stress, small, diffuse granules initially form throughout the cytoplasm. These granules then coalesce near the nucleus into larger granules that disassemble once the cellular stress is removed. Complete stress granule formation is dependent upon microtubules. Human cervical cancer (HeLa) cells, pre‐treated with nocodazole for microtubule depolymerization, formed only small, diffuse stress granules upon arsenite treatment. Upon removal of nocodazole and arsenite, the small granules coalesced near the nucleus, completing formation, prior to disassembly. An organic arsenical, ZIO‐101 (darinaparsin), as single agent also induced the formation of small, diffuse stress granules, having an effect similar to that of nocodazole/arsenite. ZIO‐101 inhibited the polymerization of microtubules both in vivo and in vitro. Upon removal of ZIO‐101, the small, diffuse stress granules completed formation prior to disassembly. In conclusion, stress granules must complete formation prior to disassembly, and completion of stress granule formation is dependent upon microtubules. Research support is provided by NIH grant RO1DK43405 and a gift of ZIO‐101 from Ziopharm.