The control of extracellular adenosine is crucial to the regulation of synaptic transmission and neuroprotection. Equilibrative nucleoside transporters (ENTs) are highly expressed in the hippocampus and widely accepted as critical regulators of adenosine tone. However, the mechanisms regulating the surface distribution and transport function of ENTs are largely unknown. Since ENT1 and ENT2 contain consensus sequences for phosphorylation by protein kinase CK2, and because this protein has been reported to regulate synaptic plasticity and ENT function in non-neuronal systems, the present thesis outlines the hypothesis that CK2-induced phosphorylation of ENTs is important for their cellular localization and thus the regulation of adenosine tone and synaptic transmission. Here, a functional interaction between adenosine CK2, ENTs and AMPA receptors in the hippocampus is reported. Western blot analysis shows that a variety of CK2 inhibitors (DMAT, TBB and DRB) significantly reduced the density of ENT1 and ENT2 proteins in hippocampal membrane fractions, suggesting that CK2-mediated phosphorylation of ENTs promotes their surface localization. In contrast, it was found that the ENT1 inhibitor NBTI significantly increased in the membrane localization of ENT1, relative to the control. Moreover, ENTs were found to immunoprecipitate with GluR1 and GluR2-containing AMPA receptors; and CK2 inhibitors caused a decrease in the membrane localization of GluR2 and GluR1 AMPA receptors. These results suggest a novel signaling complex linking CK2-regulated adenosine transport to AMPA receptor trafficking in the rat hippocampus. Although the physiological significance of these findings requires further investigation, this thesis provides insight into an adenosine regulation pathway that may be important for the regulation of synaptic transmission and neuroprotection in the rat hippocampus.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-07182011-204304 |
| Date | 25 July 2011 |
| Creators | Longmuir, Nicole |
| Contributors | Muir, Gillian, Fisher, Thomas, Mulligan, Sean, Desautels, Michel, Cayabyab, Francisco |
| Publisher | University of Saskatchewan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-07182011-204304/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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