Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles

Shuji Matsuda, Yukiko Matsuda, Erik L. Snapp, Luciano D'Adamio

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Processing of the amyloid-β (Aβ) precursor protein (APP) has been extensively studied since it leads to production of Aβ peptides. Toxic forms of Aβ aggregates are considered the cause of Alzheimer's disease (AD). On the other end, BRI2 is implicated in APP processing and Aβ production. We have investigated the precise mechanism by which BRI2 modulates APP cleavages and have found that BRI2 forms a mature BRI2 polypeptide that is transported to the plasma membrane and endosomes where it interacts with mature APP. Notably, immature forms of APP and BRI2 fail to interact. Mature BRI2 inhibits APP processing by α-, β- and γ-secretases on the plasma membrane and in endocytic compartments. Thus, BRI2 is a specific inhibitor that reduces secretases' access to APP in the intracellular compartments where APP is normally processed.

Original languageEnglish (US)
Pages (from-to)1400-1408
Number of pages9
JournalNeurobiology of Aging
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2011

Keywords

  • APP
  • Alzheimer's disease
  • BRI2
  • Familial British dementia
  • Familial Danish dementia
  • Secretases

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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