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Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing

Published version
Peer-reviewed

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Authors

Seaman, MNJ 
Mukadam, Aamir 
Breusegem, Sophia 

Abstract

The processing of amyloid precursor protein (APP) to the neurotoxic pro-aggregatory Aβ peptide is controlled by the mechanisms that govern the trafficking and localisation of APP. We hypothesised that genes involved in endosomal protein sorting could play an important role in regulating APP processing and therefore analysed ~40 novel endosome-to-Golgi retrieval genes previously identified in a genome-wide siRNA screen. We report that phospholipase D3 (PLD3), a type II membrane protein, functions in endosomal protein sorting and plays an important role in regulating APP processing. PLD3 colocalises with APP in endosomes and loss of PLD3 function results in reduced endosomal tubules, impaired trafficking of several membrane proteins and reduced association of sortilin-like 1 (SorL1) with APP.

Description

Keywords

Phospholipase D, Endosome, Amyloid precursor protein, SorL1, Alzheimer disease

Journal Title

Cellular and Molecular Life Sciences

Conference Name

Journal ISSN

1420-682X
1420-9071

Volume Title

Publisher

Springer Nature
Sponsorship
Medical Research Council (MR/L007533/1)
Medical Research Council (G0700750)
MNJS is supported by funding from the Medical Research Council (Grant no.: MR/L007533/1). Work at the Cambridge Institute for Medical Research is aided by a Wellcome Trust Strategic award.