title: APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for viability.
abstract: 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 gamma-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.
authors.affiliation: Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, Boston, MA 02215, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Hornsten
authors.forename: Jason
authors.initials: J
authors.lastname: Lieberthal
authors.forename: Shruti
authors.initials: S
authors.lastname: Fadia
authors.forename: Richard
authors.initials: R
authors.lastname: Malins
authors.forename: Lawrence
authors.initials: L
authors.lastname: Ha
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Xu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Daigle
authors.forename: Mindy
authors.initials: M
authors.lastname: Markowitz
authors.forename: Gregory
authors.initials: G
authors.lastname: O'Connor
authors.forename: Ronald
authors.initials: R
authors.lastname: Plasterk
authors.forename: Chris
authors.initials: C
authors.lastname: Li
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007814:Larva / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D018978:Molting / Q000235:genetics
chemical_list: C084891:APL-1 protein, C elegans; D016564:Amyloid beta-Protein Precursor; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins