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

Cell Biology of the Neuron: Polarity, Plasticity and Regeneration, Crete 2011
The Potential Role of the CCT Complex in the
Regulation of Long Range Axonal Transport
Kinga Bercsenyi, Guillermo Menendez, Bradley Spencer-Dene, Raphael Chaleil,
Giampietro Schiavo
Cancer Research UK, London Research Institute
As a motoneuron spans the whole size of an organism it must find effective ways
to maintain efficient communication between its different parts, ensuring the
integration of different inputs, the regulation of synaptic transmission and the
maintenance of neuronal homeostasis. Fast axonal transport constitutes the
backbone of long-distance communication in neurons, functionally connecting
distal areas with the soma and vice versa. In spite of its relevance,
characterisation of the mechanisms controlling the targeting of specific ligands,
such as growth factors and their receptors, to specific axonal transport routes
remains in its infancy.
Several subunits of the CCT chaperonin complex were found to be associated
with long-range axonal retrograde transport organelles in a proteomic screen.
These organelles carry neurotrophins and their receptors from the neuromuscular
junction to the cell soma.
The CCT complex is a multisubunit chaperonin which binds to proteins
belonging to different functional groups, including endocytosis, cytoskeleton,
chromatin remodelling and the nuclear pore complex. Mutations in CCT subunits
cause severe neurodegenerative disorders. Patients suffering from mutilating
sensory neuropathy all shared a mutation in CCT5. CCT also interacts with
polyQ-expanded huntingtin protein and inhibits its aggregation, suggesting that
this complex may have a role in the clearance of protein aggregates, the
formations of which have been associated with several neurodegenerative
diseases.
The goal of my project is to investigate the role of CCT in the regulation of the
biogenesis and transport of signalling endosomes. By characterizing the
function(s) of CCT, I plan to shed light on how alterations of CCT activity lead to
neurodegenerative disorders connected to long-range axonal transport.
Presented by: Bercsenyi, Kinga
Poster No 010
Red Session
92