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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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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427517/
https://www.ncbi.nlm.nih.gov/pubmed/27687129
http://dx.doi.org/10.1038/ncomms12976
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author 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.
author_facet 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.
author_sort Wang, Tong
collection PubMed
description 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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spelling pubmed-54275172017-05-24 Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB 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. Nat Commun Article 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. Nature Publishing Group 2016-09-30 /pmc/articles/PMC5427517/ /pubmed/27687129 http://dx.doi.org/10.1038/ncomms12976 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ 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/
spellingShingle Article
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.
Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB
title Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB
title_full Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB
title_fullStr Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB
title_full_unstemmed Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB
title_short Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB
title_sort flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and trkb
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427517/
https://www.ncbi.nlm.nih.gov/pubmed/27687129
http://dx.doi.org/10.1038/ncomms12976
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