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[2019 Spring Life Sciences & IBB Seminar]
▶Subject: Lsm12 is a novel regulator of nucleocytoplasmic transport that suppresses C9orf72 poly(GR)-dependent neurodegeneration
▶Speaker: Prof. Chunghun Lim (School of Life Sciences, UNIST)
▶Date: 4:30PM/May. 3(Fri.)/2019
▶Place: Auditorium(1F), Postech Biotech Center
Oxidative stress disrupts nucleocytoplasmic transport (NCT) by sequestrating key transport factors into cytoplasmic stress granules (SG). This has also been suggested as an important mechanism underlying the cellular pathogenesis of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). Here we identify like-Sm protein 12 (LSM12) as a neuroprotective gene that controls NCT, thereby sustaining cellular homeostasis. Drosophila mutants with loss of Lsm12 function displayed lower survival rate under oxidative stress as well as severer neurodegeneration in the ALS/FTD model of the pathogenic poly(glycine-arginine) (GR) protein derived from a human C9orf72 locus. While Lsm12 was necessary for the SG assembly induced by arsenite treatment in human neuroblastoma cells, its depletion rather exaggerated NCT defects under the oxidative stress. Lsm12 effects on NCT required neither phospho-eIF2α dependent SG assembly nor LSM12-associating protein ATAXIN-2. However, we observed a similar role of Lsm12 in suppressing poly(GR)-induced NCT phenotypes. In fact, Lsm12 depletion abolished the nucleocytoplasmic gradient of RAN proteins which is crucial for the directional control of NCT. Finally, we showed that LSM12 point-mutants found in ALS patients could not rescue Lsm12 depletion phenotypes in NCT whereas LSM12 V135I, one of the ALS-associated mutations, potently interfered with wild-type NCT. Taken together, our findings unveil evolutionarily conserved roles of LSM12 in supporting cellular homeostasis under oxidative stress and protecting neurons from the pathogenesis of C9orf72-dependent ALS/FTD.
▶Inquiry: Prof. Taekyung Kim (279-2293)
* This seminar will be given in English.
Please refrain from taking photos during seminars. *