Redundancy and divergence in the amyloid precursor protein family

FEBS Lett. 2013 Jun 27;587(13):2036-45. doi: 10.1016/j.febslet.2013.05.026. Epub 2013 May 23.

Abstract

Gene duplication provides genetic material required for functional diversification. An interesting example is the amyloid precursor protein (APP) protein family. The APP gene family has experienced both expansion and contraction during evolution. The three mammalian members have been studied quite extensively in combined knock out models. The underlying assumption is that APP, amyloid precursor like protein 1 and 2 (APLP1, APLP2) are functionally redundant. This assumption is primarily supported by the similarities in biochemical processing of APP and APLPs and on the fact that the different APP genes appear to genetically interact at the level of the phenotype in combined knockout mice. However, unique features in each member of the APP family possibly contribute to specification of their function. In the current review, we discuss the evolution and the biology of the APP protein family with special attention to the distinct properties of each homologue. We propose that the functions of APP, APLP1 and APLP2 have diverged after duplication to contribute distinctly to different neuronal events. Our analysis reveals that APLP2 is significantly diverged from APP and APLP1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / chemistry
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / physiology
  • Animals
  • Evolution, Molecular
  • Genetic Variation
  • Humans
  • Models, Genetic
  • Molecular Sequence Data
  • Phylogeny
  • Protein Processing, Post-Translational
  • Sequence Homology, Amino Acid
  • Transcription, Genetic

Substances

  • Amyloid beta-Protein Precursor