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Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad
Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad
Electronic Thesis and Dissertation Repository
PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the CRFR1 PDZ-binding motif. …
Amyloid Β Peptides, Signalling And Trafficking Of The Α7 Nicotine Receptor, Kirk Young
Amyloid Β Peptides, Signalling And Trafficking Of The Α7 Nicotine Receptor, Kirk Young
Electronic Thesis and Dissertation Repository
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 …