Investigating the TrkB Interactome during Development and in Neurodegeneration
type: CreativeWork
description: Brain-derived neurotrophic factor (BDNF) is a cardinal regulator of neuronal development, survival and synaptic plasticity, signalling via its major receptor, Tyrosine receptor kinase B (TrkB). In the developing brain, BDNF acts as a guidance cue influencing the direction of the axonal growth cone. In the mature brain, it ensures survival of neurons and synaptic plasticity. Guidance cues remodel the nascent local proteome in the developing nervous system. Recently, guidance cue receptors DCC, Neuropilin-1 and Robo2 were shown to interact with the translation machinery. Both the protein and mRNA interactions of these receptors help them to define which proteins are locally synthesized in response to stimulation. BDNF likewise regulates the local nascent proteome with high spatiotemporal resolution via TrkB activation. While there is extensive data on expression level, trafficking and signalling of TrkB, little is known about its protein and RNA interactions. We hypothesised that like DCC, Neuropilin-1 and Robo-2, TrkB shows similar interaction with the translation machinery. Immunoprecipitation studies for TrkB were performed and protein interactors were analysed by LC-MS/MS, interacting mRNAs were sequenced. A specific set of ribosomal proteins, RNA-binding proteins, rRNAs and mRNAs interacting with TrkB were detected in the embryonic mouse brain. However, in the adult mouse hippocampus, where BDNF-induced local protein synthesis mediates synaptic plasticity, no receptor-ribosome interaction was detected. This suggests a remodelling of the TrkB interactome during development and that BDNF modulates the nascent proteome in adult brain via different mechanisms. To elucidate possible new roles and regulatory mechanisms of TrkB in the mature brain, we screened for novel protein interactions in adult mouse hippocampus and cerebral synaptosomes. The TrkB protein interactome was largely composed of cytoskeleton and transport vesicle-related proteins, as well as transmembra…
abstract: Brain-derived neurotrophic factor (BDNF) is a cardinal regulator of neuronal development, survival and synaptic plasticity, signalling via its major receptor, Tyrosine receptor kinase B (TrkB). In the developing brain, BDNF acts as a guidance cue influencing the direction of the axonal growth cone. In the mature brain, it ensures survival of neurons and synaptic plasticity. Guidance cues remodel the nascent local proteome in the developing nervous system. Recently, guidance cue receptors DCC, Neuropilin-1 and Robo2 were shown to interact with the translation machinery. Both the protein and mRNA interactions of these receptors help them to define which proteins are locally synthesized in response to stimulation. BDNF likewise regulates the local nascent proteome with high spatiotemporal resolution via TrkB activation. While there is extensive data on expression level, trafficking and signalling of TrkB, little is known about its protein and RNA interactions. We hypothesised that like DCC, Neuropilin-1 and Robo-2, TrkB shows similar interaction with the translation machinery. Immunoprecipitation studies for TrkB were performed and protein interactors were analysed by LC-MS/MS, interacting mRNAs were sequenced. A specific set of ribosomal proteins, RNA-binding proteins, rRNAs and mRNAs interacting with TrkB were detected in the embryonic mouse brain. However, in the adult mouse hippocampus, where BDNF-induced local protein synthesis mediates synaptic plasticity, no receptor-ribosome interaction was detected. This suggests a remodelling of the TrkB interactome during development and that BDNF modulates the nascent proteome in adult brain via different mechanisms. To elucidate possible new roles and regulatory mechanisms of TrkB in the mature brain, we screened for novel protein interactions in adult mouse hippocampus and cerebral synaptosomes. The TrkB protein interactome was largely composed of cytoskeleton and transport vesicle-related proteins, as well as transmembra…
author: Zbiegly, Julia
language: eng
keywords: Development, Glutamate transport, Neurodegeneration, Neurotrophins, Prion disease, Protein-protein interactions, Proteome, Synapse, Translation machinery, TrkB interactome, Tyrosine receptor kinase B
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/b1385769-e16a-4bc2-bc89-72b717a99a12/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-09-29
date modified: 2026-07-22T22:24:25Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.107701