Investigating the potential interactions between glutamatergic signalling and Alix (ALG-2 interacting protein X). / Syed Salim, Sharifah S Asysyura.

2016. 240 p.

Research output: ThesisDoctoral Thesis

Unpublished

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Abstract

Previous work has identified a novel dopamine receptor interacting protein, Alix (ALG-2 (apoptosis-linked gene 2-interacting protein X), using D1 receptor C-terminal domain or D3 receptor third cytoplasmic loop as 'baits' in separate yeast two-hybrid screens. Alix is thought to be important for the stability and trafficking of dopamine receptors and is an ubiquitous adaptor protein that was first described for its capacity to bind to the calcium-binding protein, ALG-2. It is known to be involved in apoptosis, regulation of cell adhesion, protein sorting, adaptation to stress conditions, endosomal trafficking and neuronal cell death. However, the exact cellular role for this protein in neuronal signalling remains poorly understood.
There is strong evidence to support the existence of direct interactions between dopamine receptors and NMDA receptors and dopamine receptor interacting proteins such as Alix may facilitate intracellular ‘cross talk’ between both neurotransmitter signalling pathways. Furthermore, Alix has been recently found within the human postsynaptic density (PSD) and since NMDA receptors are central components of the PSD, we hypothesized that Alix may be able to influence NMDA receptor function.
We have evaluated the effects of recombinant wildtype and truncated Alix proteins in NMDA receptor function using an NMDA receptor cell death assay in transiently transfected human embryonic kidney-293 cells (HEK293). We found that coexpression of Alix had a significant effect on NMDA receptor triggered cell death and we have examined Alix expression and colocalisation with NMDAR in HEK293 cells as well as endogenous Alix expression within cultured primary cortical and hippocampal neurons. Our results suggest that Alix can influence the NMDA receptor induced cell death pathway and suggests a previously unreported role for Alix as a potential modulator of NMDA receptor function.
Original languageEnglish
QualificationPh.D.
Awarding Institution
Supervisors/Advisors
Publication statusUnpublished - 2016
This open access research output is licenced under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

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