Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/134809
Title: ROLE OF WNK SIGNALING IN NEUROGENESIS AND NEUROPATHOGENESIS
Authors: LIM WEE MENG
Keywords: WNK,neurons,GABA,signaling
Issue Date: 15-Jul-2016
Citation: LIM WEE MENG (2016-07-15). ROLE OF WNK SIGNALING IN NEUROGENESIS AND NEUROPATHOGENESIS. ScholarBank@NUS Repository.
Abstract: WNK (With no lysine [K]) kinases are regulators of cation-chloride cotransporters that set the equilibrium potential of gamma-aminobutyric acid (EGABA), thus shaping the inhibitory neurotransmission in the adult central nervous system (CNS). GABA is depolarizing in the developing CNS where it promotes neuronal maturation whereas in adulthood, GABAergic inhibition is essential for the excitation-inhibition balance in the brain. This thesis examines the role of WNK3 in regulating these two phases of GABAergic signaling. Lentiviral-mediated knockdown of WNK3 hyperpolarized EGABA and altered CCCs activity in matured neurons. Electrophysiological characterization of WNK3 knockdown hippocampal neurons showed reduced capacitance and a hyperexcitability phenotype. WNK3 is known to interact with Fox proteins, splicing factors that regulate neuronal excitability. WNK3 knockdown decreased Fox-1/2 levels and altered Kcnd3 splicing, a gene involved in neuronal excitability. Thus, these findings showed that WNK3 is involved in GABAergic signaling and excitability in neurons.
URI: http://scholarbank.nus.edu.sg/handle/10635/134809
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