Award details

RhoB and the control of neuronal plasticity

Reference	BB/C001028/1
Principal Investigator / Supervisor	Professor Brian Morris
Co-Investigators / Co-Supervisors	Dr Stuart Cobb, Professor Trevor Stone
Institution	University of Glasgow
Department	Institute of Biomedical & Life Sciences
Funding type	Research
Value (£)	273,663
Status	Completed
Type	Research Grant
Start date	05/03/2005
End date	04/09/2009
Duration	54 months

Abstract

In the CNS, synaptic morphology and glutamate receptor number are key determinants of synaptic efficiency. In peripheral cells, the Rho family of small GTP-binding proteins regulate cell morphology and endocytosis/recycling of membrane proteins, and are markedly induced by stimuli causing DNA damage. RhoB expression is also dramatically induced in association with neurotoxicity, and the level of RhoB induction correlates with the degree of neurodegeneration. In a recent BBSRC-funded project, we have discovered that RhoB is post-synaptically located in hippocampal dendritic spines, that high-frequency afferent activity in the hippocampus, which induces long-term potentiation (LTP) of synaptic function, selectively activates RhoB, and that non-selective agents which affect RhoB function dramatically modify the magnitude of LTP. Thus the evidence is highly suggestive that RhoB is involved in synaptic plasticity. Using Rho expression vectors and RhoB knockout mice, this project aims to test the hypothesis that RhoB plays a major role in determining the level of synaptic plasticity, by altering either synaptic morphology or the rate of glutamate receptor recycling, and also to determine whether RhoB enhances or suppresses neurotoxicity. The findings should significantly increase our knowledge of the molecular mechanisms of physiological and pathological plasticity in the CNS, and should be extremely relevant for our understanding of the mechanisms of learning and memory, and the neuronal response to damaging stimuli.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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