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Presenilin is required for activity and nuclear access of Notch in Drosophila

Nature volume 398, pages 522–525 (1999)Cite this article

Abstract

Presenilins are membrane proteins with multiple transmembrane domains that are thought to contribute to the development of Alzheimer's disease by affecting the processing of β-amyloid precursor protein1. Presenilins also facilitate the activity of transmembrane receptors of the LIN-12/Notch family2,3,4,5. After ligand-induced processing, the intracellular domain of LIN-12/Notch can enter the nucleus and participate in the transcriptional control of downstream target genes6,7,8,9. Here we show that null mutations in the Drosophila Presenilin gene abolish Notch signal transduction and prevent its intracellular domain from entering the nucleus. Furthermore, we provide evidence that presenilin is required for the proteolytic release of the intracellular domain from the membrane following activation of Notch by ligand.

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Figure 1: Presenilin activity is required for Notch activity.
Figure 2: Presenilin is required for nuclear access of Notch.
Figure 3: Model for LIN-12/Notch signal transduction.

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Acknowledgements

We thank J. Jiang and C.-M. Chen for the isolation and preliminary characterization of the PS alleles as neurogenic mutations; A. Adachi, R.Perez and X.-J. Qin for technical assistance; S. T. Crews, T. Lieber and P. M. Macdonald for antisera; and R. Axel, D. Brower, S.-K. Chan, H.-M. Chung and M. Zecca for advice and discussion. G.S. is an investigator and I.G. is an associate investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Departments of Genetics and Development, New York, 10032, New York, USA

    Gary Struhl

  2. Departments of Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York, 10032, New York, USA

    Gary Struhl & Iva Greenwald

  3. Departments of Biochemistry and Molecular Biophysics, New York, 10032, New York, USA

    Iva Greenwald

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Correspondence to Gary Struhl or Iva Greenwald.

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Struhl, G., Greenwald, I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398, 522–525 (1999). https://doi.org/10.1038/19091

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