Research groups

Research

We are interested in the regulation of synapses in health and disease. Our research divides into two main themes:

Example of the resolution of images of 21 DIV hippocampal neurones. In this example the neurones are virally transduced with free GFP. Note we can define spine morphology, axons and what appear to be synapses

• Investigation of the mechanisms by which neurotransmitter receptors are targeted to, retained at and removed from synapses under normal and stimulated conditions. We focus mainly on the ionotropic AMPA and kainate subtypes of glutamate receptors, which account for nearly all fast excitatory neurotransmission in the brain. Although many receptors share common biosynthetic and endocytic pathways but important specific subtype and subunit differences allow selective regulation. Increased understanding of the mechanisms of these processes will give important insights into synapse formation, stabilisation and plasticity and thus into the cellular mechanisms underlying learning and memory and some neurodegenerative diseases. To address these questions we use a wide range of cell biology approaches including viral transduction techniques and fluorophore protein tagging technology to visualise the dynamics of receptor movement in living neurones in real time.
• 

  Schematic of the protein SUMOylation cycle

  The post-translational modification SUMOylation is a major regulator of protein function that plays an important role in a wide range of cellular processes. SUMOylation involves the covalent attachment of a member of the small ubiquitin-like modifier (SUMO) family of proteins to lysine residues in specific target proteins via an enzymatic cascade analogous to, but distinct from, the ubiquitination pathway. The functional and pathophysiological implications for synaptic protein SUMOylation are far-reaching. SUMOylation has already been implicated in a diverse array of synaptopathies. Therefore, better understanding of the regulation and consequences of synaptic SUMOylation is of fundamental importance. We are working to:

  • identify and functionally characterise novel synaptic SUMO substrates
  • define how SUMOylation regulates presynaptic neurotransmitter release
  • determine the activity-dependence of SUMO and SUMO-specific protease (SENP) trafficking to synapses
  • elucidate the role of SUMOylation in regulating protein – protein interactions at synapses
  • define the roles of synaptic protein SUMOylation in ischaemia.

Group

Nadia Jaafari, Filip Konopacki, Tim Craig, Chun Gou, Kevin Wilkinson. Anja Berndt, Philip Rubin, Keri Hildick, Emi Ashikaga, Jia Luo, Paul Bishop, Fatima Girach, Fernando Josa Prado, Leo Tang

Recent publications

H. Cimarosti, E. Ashikaga, N. Jaafari, L. Dearden, P. Rubin, K.A. Wilkinson and J.M. Henley (2012) Enhanced SUMOylation and SENP-1 protein levels following oxygen and glucose deprivation in neurones J.Cereb.Blood Flow Metab. 32, 17-22.

F. Konopacki, N. Jaafari, D.L. Rocca, K.A. Wilkinson, S. Chamberlain, P. Rubin, S. Kantamneni, J.R. Mellor and J.M. Henley (2011) Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis Proc. Natl. Acad. Sci. USA. 108, 19772-7.

J.M. Henley, E.A. Barker and O.O. Glebov (2011) Routes, destinations and delays; recent advances in AMPAR trafficking. Trends in Neurosciences 34, 258-68.

K.A. Wilkinson and J.M. Henley (2010) Mechanisms, regulation and consequences of protein SUMOylation. Biochem. J. 428 (2), 133-45.

View all publications listed on the University of Bristol's publication database