NMDAR signaling facilitates the IPO5-mediated nuclear import of CPEB3.
Cytoplasmic polyadenylation element-binding protein (CPEB)3 is a nucleocytoplasm-shuttling RNA-binding protein and predominantly resides in the cytoplasm where it represses target RNA translation. When translocated into the nucleus, CPEB3 binds to Stat5b and downregulates Stat5b-dependent transcription. In neurons, the activation of N-methyl-d-aspartate receptors (NMDARs) accumulates CPEB3 in the nucleus and redistributes CPEB3 in the nucleocytoplasmic compartments to control gene expression. Nonetheless, it is unclear which karyopherin drives the nuclear import of CPEB3 and which transport direction is most affected by NMDA stimulation to increase the nuclear pool of CPEB3. Here, we have identified that the karyopherins, IPO5 and CRM1, facilitate CPEB3 translocation by binding to RRM1 and a leucine-containing motif of CPEB3, respectively. NMDAR signaling increases RanBP1 expression and reduces the level of cytoplasmic GTP-bound Ran. These changes enhance CPEB3-IPO5 interaction, which consequently accelerates the nuclear import of CPEB3. This study uncovers a novel NMDA-regulated import pathway to facilitate the nuclear translocation of CPEB3.
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Hsu-Wen
HW
Chao
Yen-Ting
YT
Lai
Yi-Ling
YL
Lu
Chi-long
CL
Lin
Wei
W
Mai
Yi-Shuian
YS
Huang
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012262:Ribonucleoside Diphosphate Reductase; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D028961:beta Karyopherins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism
C513866:CPEB3 protein, human; C107940:IPO5 protein, human; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D025521:Tumor Suppressor Proteins; D028961:beta Karyopherins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D020931:ran GTP-Binding Protein