title: The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation.
abstract: The Notch signaling pathway controls diverse cell-fate specification events throughout development. The versatility of this pathway to influence different aspects of development comes from its multiple levels of regulation. Upon ligand-induced Notch activation, the Notch intracellular domain (Notch-ICD) is released from the membrane and translocates to the nucleus, where it transduces Notch signals by regulating the transcription of downstream target genes. But the exact mechanism of translocation of Notch-ICD into the nucleus is not clear. Here, we implicate Importin-α3 (also known as karyopherin-α3) in the nuclear translocation of Notch-ICD in Drosophila. Our present analyses reveal that Importin-α3 can directly bind to Notch-ICD and loss of Importin-α3 function results in cytoplasmic accumulation of the Notch receptor. Using MARCM (Mosaic Analysis with a Repressible Cell Marker) technique, we demonstrate that Importin-α3 is required for nuclear localization of Notch-ICD. These results reveal that the nuclear transport of Notch-ICD is mediated by the canonical Importin-α3/Importin-β transport pathway. In addition, co-expression of both Notch-ICD and Importin-α3 displays synergistic effects on cell proliferation. Taken together, our results suggest that Importin-α3 mediated nuclear import of Notch-ICD may play important role in regulation of Notch signaling.
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
authors.forename: Nalani
authors.initials: N
authors.lastname: Sachan
authors.forename: Abhinava K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Mousumi
authors.initials: M
authors.lastname: Mutsuddi
authors.forename: Ashim
authors.initials: A
authors.lastname: Mukherjee
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C486341:Kap-alpha3 protein, Drosophila; C497759:N protein, Drosophila; D051880:Receptors, Notch; D028901:alpha Karyopherins