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Regulation of Mint1-dependent APP trafficking by N1-Src

Black, Hannah Lucy (2012) Regulation of Mint1-dependent APP trafficking by N1-Src. MSc by research thesis, University of York.

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterised by the accumulation of Amyloid-beta (Aβ) plaques and neurofibrillary tangles. Aβ plaques form as a result of improper trafficking and processing of the Amyloid precursor protein (APP). APP trafficking is highly spatially and temporally regulated through a complex network of protein-protein interactions. Mint1/X11α is one of four neuronal trafficking adaptor proteins that bind to the YENPTY motif in the APP C-terminus. Whilst these adaptor proteins are known to regulate APP trafficking and processing, it is as yet unclear how these interactions with APP are regulated. Previous data from the laboratory shows that Mint1 is phosphorylated on Y202 and that this phosphorylation regulates APP trafficking. Here I have further investigated the role of Mint1- Y202 phosphorylation by Src in the regulation of APP trafficking and processing. I have utilized a stable, inducible APP expressing HeLa cell line to show that disruption of Mint1-Y202 phosphorylation disrupts APP trafficking following internalisation of the protein. In addition to this, data suggests that the neuronal isoform of the kinase, N1-Src, has a higher affinity for Mint1 than its ubiquitously expressed isoform C-Src. Previous studies have shown that Mint1 overexpression results in accumulation of APP in the trans-Golgi network (TGN). Interestingly, I also see this effect and moreover, observe the recruitment of N1-Src, along with APP to the perinuclear region in a Mint1- dependent manner. Together, these data suggest Mint1 and N1-Src are recruited to regulate correct APP trafficking and processing.

Item Type: Thesis (MSc by research)
Keywords: APP, Alzheimer's, Mint1, Src
Academic Units: The University of York > Biology (York)
Depositing User: Miss Hannah Black
Date Deposited: 08 Apr 2013 10:01
Last Modified: 08 Aug 2013 08:53
URI: http://etheses.whiterose.ac.uk/id/eprint/3789

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