Nuclear transport adapts to varying heat stress in a multistep mechanism.

Appropriate cell growth conditions are limited to a narrow temperature range. Once the temperature is out of this range, cells respond to protect themselves, but temperature thresholds at which various intracellular responses occur, including nuclear transport systems, remain unclear. Using a newly developed precise temperature shift assay, we found that individual transport pathways have different sensitivities to a rise in temperature. Nuclear translocations of molecular chaperone HSP70s occur at a much lower temperature than the inhibition of Ran-dependent transport. Subsequently, importin (Imp) alpha/beta-dependent import ceases at a lower temperature than other Ran-dependent transport, suggesting that these are controlled by independent mechanisms. In vitro research revealed that the inhibition of Imp alpha/beta-dependent import is caused by the dysfunction of Imp alpha 1 specifically at lower temperature. Thus, the thermosensitivity of Imp alpha 1 modulates transport balances and enables the multistep shutdown of Ran-dependent transport systems according to the degree of heat stress.