R. Jane Rylett
Chair and Professor
 |
PH.D. University of Western Ontario |
Research in my laboratory is in cellular and molecular neurobiology, focusing predominantly on presynaptic function of cholinergic neurons. We address fundamental questions aboutthe regulation of cholinergic neurons, and how neurochemical communication may be altered in aging and disease. Cholinergic neurons control diverse physiological processes including learning and memory, sleep and movement, and their degeneration early in Alzheimer disease is key to the loss of cognitive function and attentional processing or in neuromuscular disease results in a loss of motion and respiratory failure. The main approach to our studies is with a range of methods at the cellular, molecular, proteomic and genomic levels, combined with high-resolution imaging of live cells to evaluate neuronal responses to their environment and protein trafficking events. Our recent investigations have identified mechanisms that are involved in the regulation of the cholinergic neuronal proteins choline acetyltransferase (ChAT) and choline transport (CHT) and expression of cholinergic neuronal phenotype, the crystal structure of human ChAT and structural basis of catalysis, identification of phosphorylation sites in cholinergic-specific proteins and the role of phosphorylation in the regulation of their function, and protein interactions that alter cholinergic protein function. We have also been actively involved in collaborative studies of changes in cholinergic neuron function in subjects with mild cognitive impairment and early Alzheimer disease, evaluation of effects of treatments using advanced imaging approaches and development of imaging approaches to improve diagnostic accuracy and track disease progression.
Selected Publications Kim AR, Dobransky T, *Rylett RJ and *Shilton BH (2005) Surface-entropy reduction used in the crystallization of human choline acetyltransferase. Acta Crystallographica D 61: 1306-1310. *co-corresponding authors Kim AR, *Rylett RJ and *Shilton BH (2006) Substrate binding and catalytic mechanism of human choline acetyltransferase. Biochemistry 45: 14621-14631. *co-corresponding authors Gill SK, Ishak M, Dobransky T, Haroutunian V, Davis K and Rylett RJ (2007) 82-kDa choline acetyltransferase is found in nuclei of cholinergic neurons in human brain and spinal cord, and this is altered in aging and Alzheimer disease. Neurobiology of Aging 28: 1028-1040. Pinthong M, Black SAG, Ribeiro FM, Pholpramool C, Ferguson SSG and Rylett RJ (2008) Activity and subcellular trafficking of the sodium-coupled choline transporter CHT1 is regulated acutely by peroxynitrite. Molecular Pharmacology 73: 801-812. Hristova VA, Beasley SA, Rylett RJ and Shaw GS (2009) Identification of a new Zn2+-binding domain in the Parkinson’s related E3 ligase Parkin.Journal of Biological Chemistry, 284: 14978-14986. Black SAG, Ribeiro FM, Ferguson SSG and Rylett RJ (2010) Rapid, transient effects of the protein kinase C activator PMA on activity and trafficking of the rat high-affinity choline transporter CHT.Neuroscience, 167: 765-773. Black SAG and Rylett RJ (2012) Choline transporter CHT regulation and function in cholinergic neurons.Current Medicinal Chemistry - Central Nervous System Agents in Medicinal Chemistry, 12, 114-121. Cuddy LK, Gordon AC, Black SAG, Jaworski E, Ferguson SSG and Rylett RJ (2012) Peroxynitrite alters high-affinity choline transporter CHT activity by modifying its intracellular trafficking. Journal of Neuroscience, 32: 5573-5584. Kalisch BE, Baskey JC and Rylett RJ (2012) The relationship between choline acetyltransferase and nitric oxide synthase isoform expression in Alzheimer’s disease. Journal of Alzheimer’s Disease & Parkinsonism, 2: 105-114.
