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

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    Author(s)
    Wang, Tong
    Martin, Sally
    Nguyen, Tam H
    Harper, Callista B
    Gormal, Rachel S
    Martinez-Marmol, Ramon
    Karunanithi, Shanker
    Coulson, Elizabeth J
    Glass, Nick R
    Cooper-White, Justin J
    van Swinderen, Bruno
    Meunier, Frederic A
    Griffith University Author(s)
    Karunanithi, Shanker
    Year published
    2016
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    Abstract
    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 ...
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    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.
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    Journal Title
    Nature Communications
    Volume
    7
    DOI
    https://doi.org/10.1038/ncomms12976
    Copyright Statement
    © The Author(s) 2016 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
    Subject
    Neurosciences not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/100488
    Collection
    • Journal articles

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