Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49245
Title: MECHANISTIC CHARACTERIZATION OF BNIP-H FUNCTION IN NEURON THROUGH ITS BINDING WITH ATP CITRATE LYASE
Authors: SUN JICHAO
Keywords: BNIP-H, ACL, trafficking, cholinergic, MAPK, neurite growth
Issue Date: 20-Aug-2013
Source: SUN JICHAO (2013-08-20). MECHANISTIC CHARACTERIZATION OF BNIP-H FUNCTION IN NEURON THROUGH ITS BINDING WITH ATP CITRATE LYASE. ScholarBank@NUS Repository.
Abstract: Mutations in the ATCAY/Atcay allele that encodes a brain-specific BNIP-2 family protein, BNIP-H/CAYTAXIN, are linked to ataxia and dystonia. However, the molecular mechanism underlying its function and regulation remains unclear. This thesis provides evidence that BNIP-H mediates ATP Citrate Lyase (ACL) trafficking towards PC12 neurite terminals via kinesin-1 motor, leading to enhanced secretion of acetylcholine (ACh). This process in turn activates ERK, a component of MAPK signaling module through the muscarinic ACh receptor (mAChR), thus promoting neurite outgrowth. The stimulatory effect by BNIP-H is abrogated by inhibiting the following: ACL expression, ACL activity, BNIP-H binding to kinesin, ACh secretion, ACh function, mAChR and MEK/ERK. Furthermore, BNIP-H and ACL binding synergistically recruits choline acetyltransferase at neurite terminals. BNIP-H represents a novel link in neurosignalling and neurotransmission by acting as a scaffold that regulates precise targeting of ACL and local production of ACh to modulate ERK activation in neuronal functions.
URI: http://scholarbank.nus.edu.sg/handle/10635/49245
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