Sandra Fahim

Date of Award


Degree Type


Degree Name

Master of Science


Pharmacology and Toxicology


Dr. Stephen Sean Gilbert Ferguson


Group I metabotropic glutamate receptors (mGluRl and mGluR5) are activated by glutamate, the major excitatory neurotransmitter in the brain. mGluRl/5 stimulation causes the release of calcium from intracellular stores thereby activating calcium- regulated downstream effector enzymes that produce long-lasting changes in synaptic activity that are implicated in memory, learning, and neurodegenerative diseases. Therefore, understanding the precise molecular mechanisms underlying mGluRl/5 desensitization is important in understanding the physiological response caused by these receptors. Recently, we have discovered a novel Group I mGluR-interacting protein, spinophilin. Spinophilin is a multifunctional protein that regulates the endocytosis of some GPCRs through its interaction with the receptors third intracellular loop domain. We find that spinophilin over-expression decreases agonist-stimulated internalization of mGluRla, does not affect mGluRla-dependent activation of phospholipase C leading to inositol phosphate formation, but results in attenuated ERK1/2 phosphorylation. Thus, this study provides evidence that spinophilin regulates the signalling and internalization of Group I mGluRs.



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