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


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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2016 Authors; published by Portland Press Limited Funding: BBSRC [BB/K014862/1]
Uncontrolled Keywords: Alzheimer s disease,amyloid precursor protein,Fab1,phosphatidylinositol-3,5-bisphosphate,PIKfyve,trafficking,Vac14,Biochemistry
Publication ISSN: 1470-8752
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.bioc ... ontent/44/1/185 (Publisher URL)
PURE Output Type: Article
Published Date: 2016-02-15
Published Online Date: 2016-02-09
Accepted Date: 2016-02-01
Authors: Currinn, Heather
Wassmer, Thomas



Version: Accepted Version

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