Degree
Master of Science
Program
Physiology
Supervisor
Dr. Stephen Ferguson
Abstract
The metabotropic glutamate receptor 5 (mGluR5) is a GPCR coupled to the heterotrimeric G protein Gaq/11 and activates signaling pathways important for excitatory synaptic transmission. Emerging studies reveal that Amyloid b (Ab) acts as an extracellular scaffold for mGluR5. We have identified Ca2+/Calmodulin-dependent protein Kinase IIα (CAMKIIα) as an interacting protein of mGluR5. We hypothesize that CaMKIIα plays a role in mGluR5 signaling and Ab produces differential effects on the regulation of mGluR5 by CAMKIIα. We find that overexpression of CAMKIIα significantly impairs mGluR5-mediated ERK1/2 phosphorylation but does not effect inositol phosphate formation or Ca2+ release. We find that Ab increases the amount of co-immunoprecipitated CAMKIIα to mGluR5 and can activate mGluR5-mediated ERK1/2 phosphorylation via a PKC-dependent mechanism. mGluR5 and CAMKIIα are involved in learning and memory. Furthermore, Ab and mGluR5 are implicated in Alzheimer’s disease. Thus, investigating how these proteins work together could provide insight for developing treatments for Alzheimer’s disease.
Recommended Citation
Raka, Fitore, "Regulation of Metabotropic Glutamate Receptor 5 activity by Ca2+/Calmodulin-dependent Protein Kinase IIα" (2014). Electronic Thesis and Dissertation Repository. 2408.
https://ir.lib.uwo.ca/etd/2408