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 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.
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Tong
T
Wang
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Sally
http://orcid.org/0000-0001-9294-5404
S
Martin
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Tam H
TH
Nguyen
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Callista B
CB
Harper
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Rachel S
RS
Gormal
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Ramon
R
Martínez-Mármol
Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
Shanker
S
Karunanithi
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.|School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
Elizabeth J
http://orcid.org/0000-0003-3783-6197
EJ
Coulson
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.
Nick R
NR
Glass
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.|School of Chemical Engineering, The University of Queensland, Brisbane, Queensland 4072, Australia.|Materials Science and Engineering Division, CSIRO, Clayton, Victoria 3168, Australia.
Justin J
JJ
Cooper-White
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Bruno
B
van Swinderen
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Frédéric A
FA
Meunier
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