The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation.
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-...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3698139?pdf=render |
| _version_ | 1818313529957023744 |
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| author | Nalani Sachan Abhinava K Mishra Mousumi Mutsuddi Ashim Mukherjee |
| author_facet | Nalani Sachan Abhinava K Mishra Mousumi Mutsuddi Ashim Mukherjee |
| author_sort | Nalani Sachan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T08:35:12Z |
| format | Article |
| id | doaj.art-b942fce47cff4211b130a08b812b5f80 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T08:35:12Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-b942fce47cff4211b130a08b812b5f802022-12-21T23:53:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6824710.1371/journal.pone.0068247The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation.Nalani SachanAbhinava K MishraMousumi MutsuddiAshim MukherjeeThe 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.http://europepmc.org/articles/PMC3698139?pdf=render |
| spellingShingle | Nalani Sachan Abhinava K Mishra Mousumi Mutsuddi Ashim Mukherjee The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation. PLoS ONE |
| 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. |
| title_full | The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation. |
| title_fullStr | The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation. |
| title_full_unstemmed | The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation. |
| title_short | The Drosophila importin-α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation. |
| title_sort | drosophila importin α3 is required for nuclear import of notch in vivo and it displays synergistic effects with notch receptor on cell proliferation |
| url | http://europepmc.org/articles/PMC3698139?pdf=render |
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