APL-1, a Caenorhabditis elegans protein related to the human β-amyloid precursor protein, is essential for viability

Dominant mutations in the amyloid precursor protein (APP) gene are associated with rare cases of familial Alzheimer's disease; however, the normal functions of APP and related proteins remain unclear. The nematode Caenorhabditis elegans has a single APP-related gene, apl-1, that is expressed in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-02, Vol.104 (6), p.1971-1976
Main Authors: Hornsten, Angela, Lieberthal, Jason, Fadia, Shruti, Malins, Richard, Ha, Lawrence, Xu, Xiaomeng, Daigle, Isabelle, Markowitz, Mindy, O'Connor, Gregory, Plasterk, Ronald, Li, Chris
Format: Article
Language:English
Subjects:
Adult animals
Amyloid beta-Protein Precursor - genetics
Animals
Biological Sciences
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - growth & development
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - physiology
Eggs
Humans
Larva - genetics
Larvae
Larval development
Membrane Proteins - genetics
Membrane Proteins - physiology
Molting - genetics
Muscles
Nematoda
Neurons
Phenotypes
Transgenes
Transgenic animals
Viability
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Summary:Dominant mutations in the amyloid precursor protein (APP) gene are associated with rare cases of familial Alzheimer's disease; however, the normal functions of APP and related proteins remain unclear. The nematode Caenorhabditis elegans has a single APP-related gene, apl-1, that is expressed in multiple tissues. Loss of apl-1 disrupts several developmental processes, including molting and morphogenesis, and results in larval lethality. The apl-1 lethality can be rescued by neuronal expression of the extracellular domain of APL-1. These data highlight the importance of the extracellular domain of an APP family member and suggest that APL-1 acts noncell-autonomously during development. Overexpression of APL-1 also causes several defects, including a high level of larval lethality. Decreased activity of sel-12, a C. elegans homologue of the human γ-secretase component presenilin 1, partially rescues the lethality associated with APL-1 overexpression, suggesting that SEL-12 activity regulates APL-1 activity either directly or indirectly.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0603997104