Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome

Neuron
Roberta CagnettaChristine E Holt

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.

Citations

Oct 20, 2018·Molecular Omics·Indrek Koppel, Mike Fainzilber
Jun 18, 2019·Traffic·Nadia FormicolaFlorence Besse
Aug 21, 2020·Proteomics·Aleksandra A Petelski, Nikolai Slavov
Sep 23, 2020·Open Biology·Benita Turner-BridgerJean-Michel Cioni
Sep 26, 2020·Journal of Cellular and Molecular Medicine·Xin WangTianyi Wang
Sep 30, 2020·RNA Biology·Julie Qiaojin LinChristine E Holt
Sep 27, 2018·Frontiers in Cellular Neuroscience·Kin-Mei LeungChristine E Holt
Nov 22, 2018·Frontiers in Molecular Neuroscience·Cláudio Gouveia Roque, Christine E Holt
Nov 23, 2018·Nature Protocols·Christopher S HughesJeroen Krijgsveld
Jul 5, 2019·Nature Structural & Molecular Biology·Christine E HoltErin M Schuman
Dec 12, 2019·Frontiers in Molecular Biosciences·Kavya Vinayan Pushpalatha, Florence Besse
Aug 31, 2019·Frontiers in Molecular Neuroscience·Eduardo PennaMarianna Crispino
Apr 10, 2020·Frontiers in Neuroscience·Naoki SuzukiMasashi Aoki
Oct 1, 2020·AIMS Neuroscience·Mohammad Mofatteh
Jul 22, 2019·International Journal of Molecular Sciences·Shon A KorenJose F Abisambra
Dec 31, 2019·Molecular Systems Biology·Mario LeutertJudit Villén
Sep 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Benita Turner-BridgerChristine E Holt
May 24, 2020·International Journal of Molecular Sciences·Sung Wook Kim, Kyong-Tai Kim
Sep 19, 2020·The EMBO Journal·Konstadinos MoissogluStavroula Mili
Aug 14, 2019·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Michihiro Igarashi
Nov 22, 2020·International Journal of Molecular Sciences·Eloina Corradi, Marie-Laure Baudet
Sep 27, 2020·Developmental Biology·Ashley Waldron, Mamiko Yajima
Dec 12, 2019·Cell Reports·Toshiaki ShigeokaChristine E Holt
Jan 30, 2021·Nature Neuroscience·Michael S FernandopulleMichael E Ward
Feb 18, 2020·Neuropharmacology·Adriano ChiòGabriele Mora
Aug 22, 2020·Current Opinion in Neurobiology·Joelle M Dorskind, Alex L Kolodkin
Apr 2, 2021·Journal of Proteome Research·Andres Di PaoloJosé Sotelo Silveira
Apr 16, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Livia Goto-SilvaMagno Junqueira
May 3, 2021·Molecular & Cellular Proteomics : MCP·Charlotte A G H van Gelder, Maarten Altelaar
May 4, 2021·Frontiers in Molecular Neuroscience·Erin FingletonKatherine W Roche
Oct 7, 2020·Seminars in Cell & Developmental Biology·Natássia Cristina Martins OliveiraMário Henrique Bengtson
Oct 2, 2020·Physiological Reviews·Rico SchieweckMichael A Kiebler
Jul 13, 2021·Frontiers in Cellular Neuroscience·Andres Di PaoloJosé Roberto Sotelo-Silveira
Jul 2, 2021·Frontiers in Molecular Neuroscience·Seiichi Nagano, Toshiyuki Araki
Aug 18, 2021·EMBO Reports·Kira MüntjesMichael Feldbrügge
Jul 23, 2020·Journal of Proteome Research·Matthew Waas, Thomas Kislinger
Mar 23, 2019·ACS Synthetic Biology·Huixin LuG Andrew Woolley

❮ Previous
Next ❯

Datasets Mentioned

BETA
PXD005469

Methods Mentioned

BETA
proximity ligation assay
PCA
Assay
acetylation

Software Mentioned

limma
ImageJ
R
Bioconductor
Maxquant
SP3
Perseus
DAVID
Volocity
pSILAC

Related Concepts

Related Feeds

Axon Guidance

Axon guidance is a complex neural developmental field that investigates mechanisms through which neurons send out axons to reach its target. Here is the latest research in this domain.

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.