Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome.
Publication Date
2018-07Journal Title
Neuron
ISSN
0896-6273
Publisher
Elsevier
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. (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 Labelling 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 over 100 different nascent protein species up-/down-regulated 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
Axons, Retinal Ganglion Cells, Cells, Cultured, Embryo, Nonmammalian, Animals, Xenopus laevis, Brain-Derived Neurotrophic Factor, Semaphorin-3A, Proteome, Isotope Labeling, Proteomics, Gene Expression Regulation, Mass Spectrometry, Neuronal Outgrowth, Netrin-1
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
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