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PhD Transfer Exam – Arthur Cheng (Cheng lab)
February 11, 2016 @ 1:10 pm - 2:10 pm
PhD Transfer Examination
Thursday February 11th, 1:10 pm – DV 3129, University of Toronto at Mississauga
Arthur Cheng (Cheng lab)
“ The Role of G Protein Coupled Receptor Kinases in Adult Murine Hippocampal Neurogenesis and Circadian Clock Regulation“
Abstract
G protein-coupled receptors (GPCR) detect a broad spectrum of extracellular signals at the plasma membrane, thereby modulating a wide variety of biological processes. Upon stimulation, GPCRs promote the activation of heterotrimeric G-proteins leading to its dissociation into Gα and Gβγ subunits, both of which modulate different effector systems. Agonist stimulation also triggers complex regulatory mechanisms, so the cellular responses mediated by GPCRs are usually rapidly attenuated, a process termed desensitization. Receptor phosphorylation by specific G protein-coupled receptor kinases (GRKs) plays a key role in triggering rapid desensitization. Phosphorylation of agonist-occupied GPCR by GRKs promotes the binding of cytosolic proteins termed arrestins to the receptor, resulting in the uncoupling and internalization of GPCR from G proteins. Moreover, GRKs may contribute to modulate cellular functions in a phosphorylation-independent manner due to their ability to interact with a variety of proteins involved in signalling and trafficking such as Gαq, Gβγ, clathrin, and caveolin.
The key role that GRKs play in GPCR signalling and modulation suggests that changes in their cellular complement and functionality would strongly affect GPCR function, as has been described in several diseases such as hypertension, congestive heart failure or rheumatoid arthritis. The primary objective of this proposal is to systematically investigate the function of two highly expressed GRKs – GRK2 and GRK5 – in two important biological processes and niches: 1) adult neurogenesis in hippocampal subgranular zone and 2) circadian timekeeping in suprachiasmatic nucleus.