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

Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1971-6. doi: 10.1073/pnas.0603997104. Epub 2007 Jan 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Humans
  • Larva / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Molting / genetics

Substances

  • APL-1 protein, C elegans
  • Amyloid beta-Protein Precursor
  • Caenorhabditis elegans Proteins
  • Membrane Proteins