The amyloid precursor protein (APP) binds the PIKfyve complex and modulates its function

Heather Currinn*, Thomas Wassmer

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Phosphoinositides are important components of eukaryotic membranes that are required for multiple forms of membrane dynamics. Phosphoinositides are involved in defining membrane identity, mediate cell signalling and control membrane trafficking events. Due to their pivotal role in membrane dynamics, phosphoinositide de-regulation contributes to various human diseases. In this review, we will focus on the newly emerging regulation of the PIKfyve complex, a phosphoinositide kinase that converts the endosomal phosphatidylinositol-3-phosphate [PI(3)P] to phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2)], a low abundance phosphoinositide of outstanding importance for neuronal integrity and function. Loss of PIKfyve function is well known to result in neurodegeneration in both mousemodels and human patients. Our recent work has surprisingly identified the amyloid precursor protein (APP), the central molecule in Alzheimer s disease aetiology, as a novel interaction partner of a subunit of the PIKfyve complex, Vac14. Furthermore, it has been shown that APP modulates PIKfyve function and PI(3,5)P2 dynamics, suggesting that the APP gene family functions as regulator of PI(3,5)P2 metabolism. The recent advances discussed in this review suggest a novel, unexpected, â-amyloid-independent mechanism for neurodegeneration in Alzheimer s disease.

Original languageEnglish
Pages (from-to)185-190
Number of pages6
JournalBiochemical Society Transactions
Volume44
Issue number1
Early online date9 Feb 2016
DOIs
Publication statusPublished - 15 Feb 2016

Bibliographical note

© 2016 Authors; published by Portland Press Limited
Funding: BBSRC [BB/K014862/1]

Keywords

  • Alzheimer s disease
  • amyloid precursor protein
  • Fab1
  • phosphatidylinositol-3,5-bisphosphate
  • PIKfyve
  • trafficking
  • Vac14

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