title: The secreted Alzheimer-related amyloid precursor protein fragment has an essential role in C. elegans.
abstract: Mutations in the gene encoding the amyloid precursor protein (APP) or the enzymes that process APP are correlated with familial Alzheimer disease. Alzheimer disease is also associated with insulin resistance (type 2 diabetes). In our recently published study, ( 1)  we obtained genetic evidence that the extracellular fragment of APL-1, the C. elegans ortholog of human APP, may act as a signaling molecule to modulate insulin and nuclear hormone pathways in C. elegans development. In addition, independent of insulin and nuclear hormone signaling, high levels of the extracellular fragment of APL-1 (sAPL-1) leads to a temperature-sensitive embryonic lethality, which is dependent on activity of a predicted receptor protein tyrosine phosphatase (MOA-1/R155.2). Furthermore, this embryonic lethality is enhanced by knockdown of a predicted prion-like protein (pqn-29). The precise molecular mechanisms underlying these processes remain to be determined. Here, we present hypothetical models as to how sAPL-1 signaling influences metabolic and developmental pathways. Together, with previous findings in mammals that the extracellular domain of mammalian APP (sAPP) binds to a death-receptor, ( 2)  our findings support the model that sAPP signaling affects critical biological processes.
authors.affiliation: Joslin Diabetes Center, Harvard Stem Cell Institute, and Department of Genetics, Harvard Medical School, Boston, MA USA.
authors.forename: Collin Y
authors.initials: CY
authors.lastname: Ewald
authors.forename: Chris
authors.initials: C
authors.lastname: Li
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C084891:APL-1 protein, C elegans; D016564:Amyloid beta-Protein Precursor; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins