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

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

  • Cell Mol Life Sci. 2018 Jul;75(14):2613-2625. doi: 10.1007/s00018-018-2752-9.
Aamir S Mukadam 1,  Sophia Y Breusegem 1,  Matthew N J Seaman 2
Affiliations

Affiliations

  • 1 Cambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK.
  • 2 Cambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK. mnjs100@cam.ac.uk.
PMID: 29368044 DOI: 10.1007/s00018-018-2752-9
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 co-localises 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 with APP.

Keywords

Alzheimer disease; Amyloid precursor protein; Endosome; Phospholipase D; SorL1.

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