CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab
CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab
CELL BIOLOGY OF THE NEURON Polarity ... - Tavernarakis Lab
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Cell Biology of the Neuron: <strong>Polarity</strong>, Plasticity and Regeneration, Crete 2011<br />
Tracking Autophagosome Dynamics in Primary<br />
Neurons<br />
Sandra Maday, Karen Wallace, Erika Holzbaur<br />
University of Pennsylvania School of Medicine<br />
Autophagy is a lysosomal degradation process that is particularly important in<br />
post-mitotic cells such as neurons. Inhibition of autophagy leads to<br />
neurodegeneration (Komatsu et al., 2006; Hara et al., 2006). To determine the<br />
dynamics of autophagosomes in neurons, we isolated dorsal root ganglion<br />
neurons from transgenic mice expressing the autophagosome marker GFP-LC3<br />
and performed live-cell imaging. Autophagosomes displayed robust motility<br />
along neuronal processes, strongly biased toward the retrograde direction (82 ± 2<br />
[± SEM] % of autophagosomes were retrograde). Autophagosomes moved at an<br />
average velocity of 0.45 ± 0.01 (± SEM) µm/sec, exhibited few reversals in<br />
direction, and paused ~10% of their journey. Disruption of dynein/dynactin<br />
function arrested autophagosome motility. These results suggest that<br />
autophagosomes are robustly transported along the neurite in a predominantly<br />
retrograde direction by the microtubule motor cytoplasmic dynein. This<br />
unidirectional transport of autophagosomes in the axon is distinct from the<br />
motility exhibited by other organelles such as lysosomes that predominantly<br />
move bidirectionally. To determine the maturation state of autophagosomes in the<br />
axon, we analyzed the composition of autophagosomes with regard to lysosomal<br />
markers. Our results support a model in which autophagosomes undergoing<br />
active transport along the neurite are acidified but have not yet fused with<br />
lysosomes. This model is distinct from the prevailing paradigm based on work in<br />
non-polarized cells. Our data suggest that neurons, due to their unique<br />
morphology, may have specialized pathways where the spatial and temporal<br />
dynamics of organelles may be linked to their function.<br />
Presented by: Maday, Sandra<br />
149<br />
Poster No 067<br />
Red Session