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Rab10 regulates the sorting of internalised TrkB for retrograde axonal transport

Lazo, Oscar Marcelo; Schiavo, Giampietro; (2023) Rab10 regulates the sorting of internalised TrkB for retrograde axonal transport. eLife , 12 , Article e81532. 10.7554/eLife.81532. Green open access

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Abstract

Neurons process real-time information from axon terminals to coordinate gene expression, growth, and plasticity. Inputs from distal axons are encoded as a stream of endocytic organelles, termed signalling endosomes, targeted to the soma. Formation of these organelles depends on target-derived molecules, such as brain-derived neurotrophic factor (BDNF), which is recognised by TrkB receptors on the plasma membrane, endocytosed, and transported to the cell body along the microtubules network. Notwithstanding its physiological and neuropathological importance, the mechanism controlling the sorting of TrkB to signalling endosomes is currently unknown. In this work, we use primary mouse neurons to uncover the small GTPase Rab10 as critical for TrkB sorting and propagation of BDNF signalling from axon terminals to the soma. Our data demonstrate that Rab10 defines a novel membrane compartment that is rapidly mobilised towards the axon terminal upon BDNF stimulation, enabling the axon to fine-tune retrograde signalling depending on BDNF availability at the synapse. These results help clarifying the neuroprotective phenotype recently associated to Rab10 polymorphisms in Alzheimer's disease and provide a new therapeutic target to halt neurodegeneration.

Type: Article
Title: Rab10 regulates the sorting of internalised TrkB for retrograde axonal transport
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.81532
Publisher version: https://doi.org/10.7554/eLife.81532
Language: English
Additional information: Copyright © 2023, Lazo and Schiavo. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: Brain-derived neurotrophic factor, KIF13B, mouse, neuroscience, neurotrophin, signalling endosome, small GTPases
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10166582
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