Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB

Axonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic si...

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Published in:Nature communications 2016-09, Vol.7 (1), p.12976-12976, Article 12976
Main Authors: Wang, Tong, Martin, Sally, Nguyen, Tam H., Harper, Callista B., Gormal, Rachel S., Martínez-Mármol, Ramon, Karunanithi, Shanker, Coulson, Elizabeth J., Glass, Nick R., Cooper-White, Justin J., van Swinderen, Bruno, Meunier, Frédéric A.
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Language:English
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Bioengineering
Brain-derived neurotrophic factor
Cholera
Humanities and Social Sciences
Kinases
Labeling
Localization
Microscopy
multidisciplinary
Nanotechnology
Science
Science (multidisciplinary)
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Summary:Axonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic activity markedly increased the flux of plasma membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured in microfluidic devices, and live Drosophila larval motor neurons. Electron and super-resolution microscopy analyses revealed that the fast-moving sub-diffraction-limited CTB carriers contained the TrkB neurotrophin receptor, transiently activated by synaptic activity in a BDNF-independent manner. Pharmacological and genetic inhibition of TrkB activation selectively prevented the coupling between synaptic activity and the retrograde flux of signalling endosomes. TrkB activity therefore controls the encoding of synaptic activity experienced by nerve terminals, digitalized as the flux of retrogradely transported signalling endosomes. Signalling endosomes are known to be essential for neuronal survival. Here the authors show that, in cultured hippocampal neurons and live Drosophila larval motor neurons, neuronal activity increases the retrograde flux of signalling endosomes, and this coupling depends on TrkB activation.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms12976