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. 2013 Jul 1;8(7):e68247. doi: 10.1371/journal.pone.0068247. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Mutation
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism*

Substances

  • Drosophila Proteins
  • Kap-alpha3 protein, Drosophila
  • N protein, Drosophila
  • Receptors, Notch
  • alpha Karyopherins

Grants and funding

N.S. and A.K.M. were supported by fellowships from Indian Council of Medical Research and Council of Scientific and Industrial Research, India, respectively. This work was supported by grants from Department of Science and Technology, India and Department of Biotechnology, India to A.M. and M.M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.