The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions,including cell morphology,elasticity,migration,organelle localization,and resistance against me...The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions,including cell morphology,elasticity,migration,organelle localization,and resistance against mechanical or pathological stress.Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus.Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking,limiting in-depth studies on vimentin function and potential therapeutic applications.Here,we verified that a commercially available small molecule,trametinib,is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational regulation.Further evidence confirmed its low cytotoxicity and similar effects on different cell types.Importantly,Trametinib has no impact on the other two cytoskeletal systems,actin filaments and the microtubule network.Moreover,Trametinib regulates vimentin network dispersion rapidly and efficiently,with effects persisting for up to 48 h after drug withdrawal.We also ruled out the possibility that Trametinib directly affects the phosphorylation level of vimentin.In summary,we identified an unprecedented regulator Trametinib,which is capable of spreading the vimentin network toward the cell periphery,and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.展开更多
基金supported by the National Natural Science Foundation of China(92354301,32222022,32300569,and 92054104)R&D Program of Guangzhou National Laboratory(GZNL2023A03004)+2 种基金Key Research and Development Program,the Ministry of Science and Technology of China(2022YFC2303502 and 2021YFC2300204)the Natural Science Foundation of Shanghai(23ZR1470900)Youth Innovation Promotion Association,Chinese Academy of Sciences.
文摘The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions,including cell morphology,elasticity,migration,organelle localization,and resistance against mechanical or pathological stress.Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus.Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking,limiting in-depth studies on vimentin function and potential therapeutic applications.Here,we verified that a commercially available small molecule,trametinib,is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational regulation.Further evidence confirmed its low cytotoxicity and similar effects on different cell types.Importantly,Trametinib has no impact on the other two cytoskeletal systems,actin filaments and the microtubule network.Moreover,Trametinib regulates vimentin network dispersion rapidly and efficiently,with effects persisting for up to 48 h after drug withdrawal.We also ruled out the possibility that Trametinib directly affects the phosphorylation level of vimentin.In summary,we identified an unprecedented regulator Trametinib,which is capable of spreading the vimentin network toward the cell periphery,and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.
