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Pdz Protein Regulation Of Β-Arrestin Recruitment And Gpcr Trafficking, Sarah Gupta Dec 2016

Pdz Protein Regulation Of Β-Arrestin Recruitment And Gpcr Trafficking, Sarah Gupta

Electronic Thesis and Dissertation Repository

β-arrestins are versatile adaptor proteins that play a vital role in regulation of G protein coupled receptor (GPCR) trafficking and signalling properties. PDZ proteins have previously been shown to modulate β-arrestin2 recruitment and receptor internalization for many GPCRs including Corticotropin-Releasing Factor Receptor 1 (CRFR1), a receptor whose antagonists have been shown to demonstrate both anxiolytic- and antidepressant-like effects. Further characterization of the interplay between β-arrestins and PDZ proteins may aid in determining a potential mechanism for PDZ protein regulation of GPCR trafficking. Our findings suggest that PDZ proteins PSD-95, MAGI1, and PDZK1 complex with β-arrestin2 by interacting via the PDZ …


Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla Oct 2016

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR1 and 5-HT2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT2A/CRs. The first purpose of this thesis was …


Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad Aug 2016

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. …


The Role Of Forebrain Cholinergic Signalling In Regulating Hippocampal Function And Neuropathology, Mohammed Al-Onaizi Jun 2016

The Role Of Forebrain Cholinergic Signalling In Regulating Hippocampal Function And Neuropathology, Mohammed Al-Onaizi

Electronic Thesis and Dissertation Repository

Cholinergic dysfunction has been associated with cognitive abnormalities in a variety of neurodegenerative and neuropsychiatric disorders, including Alzheimer’s Disease (AD). Cumulative use of drugs with anticholinergic activity is associated with increased risk for dementia and AD. Also, cholinergic function has been implicated in predicting the development of key neuropathological hallmarks seen in AD. However, the relationship between cholinergic dysfunction and conservation of cognitive ability as well as neuronal cell maintenance is not fully understood. Here, we tested how information processing and distinct molecular mechanisms associated with AD are regulated by cholinergic tone in genetically-modified mice in which cholinergic transmission was …


Cannabinoid Cb1 Transmission In The Mesolimbic Reward Pathway, Tasha Ahmad Apr 2016

Cannabinoid Cb1 Transmission In The Mesolimbic Reward Pathway, Tasha Ahmad

Electronic Thesis and Dissertation Repository

Cannabinoid CB1 receptor (CB1R) transmission within the mesocorticolimbic system plays an important role in forming associative memories, and processing both positive and negative experiences. Opiates generally produce potent rewarding effects and previous evidence suggests that CB1 transmission may modulate the neural reward circuitry involved in opiate reward processing. The ventral tegmental area (VTA), medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and Nucleus Accumbens (NA) are all implicated in opiate-reward processing, contain high levels of CB1 receptors, and are all modulated by dopamine (DA). Although, CB1 transmission within these areas has been heavily implicated in associative memory and learning, the potential …


Examining The Role Of Atrx In Astrocytes, Haley Mcconkey Jan 2016

Examining The Role Of Atrx In Astrocytes, Haley Mcconkey

Electronic Thesis and Dissertation Repository

Astrocytes perform many homeostatic roles in the brain while supplying metabolites to neurons and mediating synaptic transmission. The current study explored a possible role of the Atrx gene in astrocytes. Hypomorphic mutations in this gene cause the ATR-X intellectual disability syndrome. Deletion of Atrx in the forebrain leads to an apparent increase in reactive astrocytes, potentially caused by the high level of neuroprogenitor cell death. To avoid such non cell-autonomous effects on astrocytes, we generated mice with inducible conditional inactivation of Atrx in astrocytes. Preliminary analysis two weeks following induction of Atrx gene deletion revealed variably lower expression of Connexin …