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Presenilin is required for proper morphology and function of neurons in C. elegans

Nature volume 406, pages 306–309 (2000)Cite this article

Abstract

Mutations in the human presenilin genes cause the most frequent and aggressive forms of familial Alzheimer's disease (FAD)1. Here we show that in addition to its role in cell fate decisions in non-neuronal tissues2,3,4, presenilin activity is required in terminally differentiated neurons in vivo. Mutations in the Caenorhabditis elegans presenilin genes sel-12 and hop-1 result in a defect in the temperature memory of the animals. This defect is caused by the loss of presenilin function in two cholinergic interneurons that display neurite morphology defects in presenilin mutants. The morphology and function of the affected neurons in sel-12 mutant animals can be restored by expressing sel-12 only in these cells. The wild-type human presenilin PS1, but not the FAD mutant PS1 A246E, can also rescue these morphological defects. As lin-12 mutant animals display similar morphological and functional defects to presenilin mutants, we suggest that presenilins mediate their activity in postmitotic neurons by facilitating Notch signalling. These data indicate cell-autonomous and evolutionarily conserved control of neural morphology and function by presenilins.

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Figure 1: Tracking of animals on a radial temperature gradient.
Figure 2: AIY interneuron morphology in sel-12, wild-type, lin-12 and hop-1;sel-12 mutant animals.

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Acknowledgements

Some strains used in this study were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. We thank I. Greenwald, E. Lambie and H. R. Horvitz for strains; R. Barstead for cDNA libraries; O. Hobert and A. Fire for plasmids and R. Donhauser and M. Grim for technical assistance. We also thank I. Mori and H. Kagoshima for their help with interpreting thermotaxis data, and C. Haass and the members of our lab for discussions and for critically reading the manuscript. Part of this work was supported by grants from the DFG to R.B. and from EMBO to B.L.

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  1. Genzentrum, Ludwig-Maximilians-Universitaet , Feodor-Lynen-Strasse 25, Munich, D-81377, Germany

    Nicole Wittenburg, Stefan Eimer, Bernard Lakowski, Sascha Röhrig & Ralf Baumeister

  2. EleGene GmbH, Am Klopferspitz 19, Martinsried, D-82152, Germany

    Claudia Rudolph

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Correspondence to Ralf Baumeister.

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Wittenburg, N., Eimer, S., Lakowski, B. et al. Presenilin is required for proper morphology and function of neurons in C. elegans. Nature 406, 306–309 (2000). https://doi.org/10.1038/35018575

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