Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing
Cellular and Molecular Life Sciences
MetadataShow full item record
Seaman, M., Mukadam, A., & Breusegem, S. (2018). Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing. Cellular and Molecular Life Sciences https://doi.org/10.1007/s00018-018-2752-9
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.
Phospholipase D, Endosome, Amyloid precursor protein, SorL1, Alzheimer disease
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.
External DOI: https://doi.org/10.1007/s00018-018-2752-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/270876
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/