Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome.
Authors
Cagnetta, Roberta
Frese, Christian K
Shigeoka, Toshiaki
Krijgsveld, Jeroen
Holt, Christine E
Publication Date
2018-07-11Journal Title
Neuron
ISSN
0896-6273
Publisher
Elsevier BV
Volume
99
Issue
1
Pages
29-46.e4
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Cagnetta, R., Frese, C. K., Shigeoka, T., Krijgsveld, J., & Holt, C. E. (2018). Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome.. Neuron, 99 (1), 29-46.e4. https://doi.org/10.1016/j.neuron.2018.06.004
Abstract
Axonal protein synthesis and degradation are rapidly regulated by extrinsic signals during neural wiring, but the full landscape of proteomic changes remains unknown due to limitations in axon sampling and sensitivity. By combining pulsed stable isotope labeling of amino acids in cell culture with single-pot solid-phase-enhanced sample preparation, we characterized the nascent proteome of isolated retinal axons on an unparalleled rapid timescale (5 min). Our analysis detects 350 basally translated axonal proteins on average, including several linked to neurological disease. Axons stimulated by different cues (Netrin-1, BDNF, Sema3A) show distinct signatures with more than 100 different nascent protein species up- or downregulated within the first 5 min followed by further dynamic remodeling. Switching repulsion to attraction triggers opposite regulation of a subset of common nascent proteins. Our findings thus reveal the rapid remodeling of the axonal proteomic landscape by extrinsic cues and uncover a logic underlying attraction versus repulsion.
Keywords
axon, axon guidance, chemotropic response, extrinsic cues, growth cone, local protein synthesis, neural wiring, pSILAC-SP3, proteomics, retinal ganglion cell, Animals, Axons, Brain-Derived Neurotrophic Factor, Cells, Cultured, Embryo, Nonmammalian, Gene Expression Regulation, Isotope Labeling, Mass Spectrometry, Netrin-1, Neuronal Outgrowth, Proteome, Proteomics, Retinal Ganglion Cells, Semaphorin-3A, Xenopus laevis
Sponsorship
BBSRC (1366878)
Wellcome Trust (085314/Z/08/Z)
European Research Council (322817)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1016/j.neuron.2018.06.004
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283500
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk
The following licence files are associated with this item: