Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

R. Jane Rylett

Abstract

The α7 nicotinic acetylcholine receptor (nAChR) is an ionotropic receptor for the neurotransmitter acetylcholine and its precursor, choline. Interestingly, α7 nAChR binds amyloid β 42 (Aβ42) peptide, which has a primary role in Alzheimer’s disease pathology. Aβ42 peptide forms aggregates and different structural forms elicit different physiological outcomes. Oligomeric, fibrillar and non-aggregated preparations of Aβ42 were characterized by atomic force microscopy. Immunoblotting of neuronal cells exposed to these preparations determined oligomeric aggregates of Aβ42 mediate ERK1/2 intracellular signalling through α7 nAChR. Cell surface ionotropic receptors are regulated through endocytosis to maintain the integrity of neurotransmission. Cellular pathways for endocytosis of α7 nAChR are not fully elucidated. Immunocytochemistry, fluorochrome-labelled proteins, and laser-scanning confocal microscopy identified a clathrin-independent flotillin 1- or caveolin 1α-associated pathway for α7 nAChR endocytosis. These studies identify a biologically important form of Aβ42 relevant to α7 nAChR intracellular signalling and an endocytosis pathway for subcellular regulation of α7 nAChR.


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