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Drosophila Appl Gene and APPL Protein: A Model System to Study the Function of the APP Protein Family

  • Conference paper
Amyloid Protein Precursor in Development, Aging and Alzheimer’s Disease

Part of the book series: Research and Perspectives in Alzheimer’s Disease ((ALZHEIMER))

Summary

Drosophila Amyloid precursor protein-like (Appl) gene encodes a protein product, APPL, similar to the β-amyloid precursor protein (APP) associated with Alzheimer’s disease. The Drosophila APPL protein is neural-specific and is first detected in developing neurons concomitant with axonogenesis. APPL immunoreactivity is observed in neuronal cell bodies and in axons of both immature and mature neurons. Similar to APP, APPL is synthesized as a membrane-associated glycosylated precursor protein that is rapidly converted into a secreted form that lacks the cytoplasmic domain.

To understand the in vivo function of the APPL protein, we have taken a neurogenetic approach. Flies deleted for the Appl gene have been generated. These flies are viable, fertile and morphologically normal, yet they exhibit subtle behavioral deficits. The fast phototaxis defect in mutant Appl flies that lack APPL protein can be partially rescued by transgenes expressing the wild-type APPL protein. Furthermore, transgenes expressing the human APP protein show a level of rescue similar to the transgenes expressing APPL. Our analyses suggest a conserved ancestral function for the APP class of proteins in the nervous system. We discuss the implications of current functional studies on the APP proteins and how the Drosophila system could facilitate the in vivo analysis of the function of this class of proteins.

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Authors and Affiliations

  1. Biology Department and Center for Complex Systems, Brandeis University, Waltham, MA, 02254, USA

    K. White

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  1. K. White
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  2. L. Luo
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  3. T. Aigaki
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  4. M. Monastirioti
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Editor information

Editors and Affiliations

  1. Department of Pathology, The University of Melbourne and The Mental Health Research Institute of Victoria, Parkville, Victoria, 3025, Australia

    C. L. Masters M.D.

  2. Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany

    K. Beyreuther Ph.D.

  3. Hôpital Neurologique, 59, Bld Pinel, 69003, Lyon, France

    M. Trillet Prof.

  4. Fondation IPSEN, 24, rue Erlanger, 75781, Paris, France

    Y. Christen Ph.D.

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© 1994 Springer-Verlag Berlin Heidelberg

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White, K., Luo, L., Aigaki, T., Monastirioti, M. (1994). Drosophila Appl Gene and APPL Protein: A Model System to Study the Function of the APP Protein Family. In: Masters, C.L., Beyreuther, K., Trillet, M., Christen, Y. (eds) Amyloid Protein Precursor in Development, Aging and Alzheimer’s Disease. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-01135-5_2

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  • DOI: https://doi.org/10.1007/978-3-662-01135-5_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-01137-9

  • Online ISBN: 978-3-662-01135-5

  • eBook Packages: Springer Book Archive

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