| Title | Does mitogen-activated protein kinase phosphatases (MKP-2) play a critical role in regulating neurotransmitter release and synaptic transmission? |
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| Supervisors | Trevor Bushell Gwyn Gould |
| Research Area | Research group: Neuroscience & Mental Health Key words: MKP-2, synaptic vesicles, neurotransmitter, synaptic transmission. |
| Description | A role for mitogen-activated protein kinases (MAPKs) is well established in physiological cell function as well as in certain disease states1. Recently, there has been growing interest in the signalling systems which control MAPK function, especially the attenuation of their activity. One family of proteins that contribute to this process is the mitogen-activated protein kinase phosphatases (MKPs). There is significant interest in MKPs especially in relation to their role in development, the immune system and cancer2,3. However, there is a significant gap in our knowledge in relation to their function in the central nervous system (CNS). Currently, our limited knowledge is restricted to MKP-1 function in the brain. However, utilising a novel mouse knockout of the Dusp4 gene encoding MKP-2, we have shown that MKP-2 alters glutamatergic synaptic transmission in two different brain regions that contributes to altered performance in memory tasks and reward processing4,5. Hence, we hypothesise that MKP-2 is important in the regulation of vesicles at the presynaptic active zone. Thus the aim of this project is test the this hypothesis to examine the following research questions: 1. What presynaptic targets are modulated by MKP-2 deletion? 2. Are the observed effects restricted to glutamatergic synapses? 3. Does MKP-2 regulate vesicular release in all cell types or just neurons? Answer to these questions will identify the role of MKP-2 in vesicle docking and determine the importance of MKP-2 in neurotransmitter release. |
| Techniques Used | Phospho-proteomic analysis, immunohistochemistry, cell culture, electrophysiology, qPCR & western blotting. |
| References | 1. Harper & Wilkie Exp Op Ther Targets (2003) 7:187-200 2. Al-Mutairi et al., PLoS Pathog (2010) 6:e1001192. 3. Lawan et al., J Biol Chem (2011) 286:12933-43. 4. Abdul Rahman et al., J Neurosci (2016) 36: 2348-54. 5. Pytka et al., EJN (2020) Accepted in press. DOI: 10.1111/ejn.14688. |
| Conditions | Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a relevant discipline such as immunology, pharmacology, neuroscience in addition to receipt of satisfactory references and an IELTS score of 6.5 where appropriate. |
| Bench Fee | Running costs of £10000 p.a. will be associated with this project in addition to University tuition fees. |
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