The Meunier laboratory at the Queensland Brain Institute had a productive year in 2013. They were awarded two grants to fund their research into neuronal communication and survival. In 2013, the laboratory published eight papers investigating topics like the role of myosin VI in neuroexocytosis and the regulation of neuroexocytosis by Munc18-1. They also demonstrated that inhibition of PIKfyve activity leads to neuronal cell death by disrupting autophagy, implicating this pathway in neurodegenerative diseases. The laboratory continued to study vesicular trafficking and collaborated with other researchers on projects involving neurotoxin transport in neurons and dynamin inhibitors.

1. Queensland Brain Institute 2013 Annual Report

2. QBI ANNUAL REPORT4
DISCOVERY

3. Mobile autophagosomes in neuronal
networks.
2013 was a year of many achievements for the
Meunier laboratory, including the award of two
grants, namely a National Health and Medical
Research Council Project grant and an Australian
Research Council LIEF grant to equip QBI with
some of the most exciting new technologies
in super resolution microscopy. In 2013, the
laboratory published eight peer-reviewed
publications and was asked to join the Clem Jones
Centre for Ageing Dementia Research (CJCADR).
The team has continued to pursue its work into
the mechanism of neuroexocytosis. This year
the group published the discovery that Myosin
VI plays a key role in capturing secretory vesicles
on the cortical actin network in an activity-de-
pendent manner (Journal of Cell Biology). They
also revealed that Munc18-1 not only controls the
delivery of Syntaxin-1 to the plasma membrane
but also regulates neuroexocytosis itself through
a key role of its domain 3a (Journal of Cell
Science). Additionally, they showed a novel type
of plasticity allows filopodial extensions to create
new release sites in response to secretagogue
stimulation (Journal of Neuroscience).
In terms of vesicular trafficking, the Meunier
laboratory demonstrated that pharmacological
inhibition of PIKfyve activity leads to an apopto-
sis-independent neuronal cell death, implicating
a dysregulation of autophagy. This pathway is
thought to be involved in a number of neuro-
degenerative diseases, including Charcot-Marie
Tooth and motor neuron disease (PLOS ONE).
The group investigated the traffic of synthetic
self-assembling clostridial chimera neurotoxin in
neurons in collaboration with Professor Bazbek
Davletov (MRC Laboratory of Molecular Biology,
UK). They also reviewed the literature on the
potential of blocking endocytic pathways to
counteract pathogens internalisation (Trends
in Cell Biology) and pursued their collabora-
tion with Professor Phillip Robinson (University
of Sydney) and Professor Adam McCluskey
(University of Newcastle) on a range of highly
effective dynamin inhibitors (Traffic).
The mechanism underpinning neuronal communication and survival
2013 Laboratory Members L-R: Frederic Meunier, Rachel Gormal, Callista Harper, Ravikiran Kasula, David Kvaskov, Regine Low, Nancy Malintan, Sally Martin, Nika Mohannak, Vinod Narayana,
Tam Hong Nguyen, Shona Osborne, Andreas Papadopulos, Vanesa Tomatis, Tong (Iris) Wang. Not pictured: Adekunle Bademosi, Shi Min (Priscilla) Goh. Background: Super-resolution
microscopy enables the visualisation and tracking of lipid molecules on the plasma membrane. The movements of cholera toxin, which binds to the ganglioside GM1, are shown. Studying
the diffusion of these individual molecules provides information on how the plasma membrane responds to stimuli. Image: Callista Harper.
QBI ANNUAL REPORT40
Laboratory Head Associate Professor Frederic Meunier*