CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab

Cell Biology of the Neuron: Polarity, Plasticity and Regeneration, Crete 2011
Defining Roles of PKMzeta in AMPA Receptor
Trafficking
Ellen Barker 1 , Jeremy Henley
1 University of Bristol
Synaptic plasticity, the modulation of communication efficacy at synapses shapes
the neural networks thought to encode memories. Long term potentiation (LTP),
the persistent enhancement in synaptic communication, is one such type of
plasticity. LTP has two main mechanistically distinct phases, an induction (early)
and a maintenance (late) phase (E-LTP, L-LTP) thought to be analogous to the
processes of initial learning and long-term memory storage. AMPA receptors
(AMPAR) mediate the majority of fast excitatory transmission in the brain, so
changes in their expression at synapses underlie synaptic plasticity, with an
increase in AMPAR number or conductivity leading to LTP. A brain-specific
atypical Protein kinase C isoform, PKMζ has been shown to be both necessary
and sufficient for L-LTP, but not E-LTP. Perfusion of ZIP, a specific inhibitor of
PKMζ into hippocampi of live rats prevents memories of a task persisting beyond
about 10 minutes, and completely erases pre-established memories. As well as
showing PKMζ is a key factor in memory formation; these studies provide
compelling evidence for links between the biphasic models of LTP and of
memory formation. I am interested in the mechanisms of PKMzeta-dependent
AMPAR trafficking on a molecular level using cultured neurons. I show that ZIP
decreases surface expression of GluR2 but not GluR1, although rates of
endocytosis of both are increased. Since GluR1 and GluR2 subunits have distinct
roles and trafficking patterns in E-LTP and L-LTP, I hope to better define the
roles of PKMζ in the context of these phases by characterising endo- and exocytic
events, as well as identifying interactions with other proteins involved.
Presented by: Barker, Ellen
Poster No 004
Red Session
86