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Coupled local translation and degradation regulate growth cone collapse.

TitleCoupled local translation and degradation regulate growth cone collapse.
Publication TypeJournal Article
Year of Publication2015
AuthorsDeglincerti A, Liu Y, Colak D, Hengst U, Xu G, Jaffrey SR
JournalNat Commun
Volume6
Pagination6888
Date Published2015 Apr 22
ISSN2041-1723
KeywordsAnimals, Axons, Blotting, Western, Electroporation, Embryo, Mammalian, Ganglia, Spinal, Growth Cones, HEK293 Cells, Hippocampus, Humans, Mice, Nerve Growth Factor, Neurons, PC12 Cells, Proteasome Endopeptidase Complex, Protein Biosynthesis, Rats, Rats, Sprague-Dawley, rhoA GTP-Binding Protein, RNA, Messenger, Semaphorin-3A, Spinal Cord, Ubiquitin-Protein Ligases, Ubiquitination
Abstract

Local translation mediates axonal responses to Semaphorin3A (Sema3A) and other guidance cues. However, only a subset of the axonal proteome is locally synthesized, whereas most proteins are trafficked from the soma. The reason why only specific proteins are locally synthesized is unknown. Here we show that local protein synthesis and degradation are linked events in growth cones. We find that growth cones exhibit high levels of ubiquitination and that local signalling pathways trigger the ubiquitination and degradation of RhoA, a mediator of Sema3A-induced growth cone collapse. Inhibition of RhoA degradation is sufficient to remove the protein-synthesis requirement for Sema3A-induced growth cone collapse. In addition to RhoA, we find that locally translated proteins are the main targets of the ubiquitin-proteasome system in growth cones. Thus, local protein degradation is a major feature of growth cones and creates a requirement for local translation to replenish proteins needed to maintain growth cone responses.

DOI10.1038/ncomms7888
Alternate JournalNat Commun
PubMed ID25901863
PubMed Central IDPMC4408908
Grant ListR01 MH096702 / MH / NIMH NIH HHS / United States
R01 NS056306 / NS / NINDS NIH HHS / United States
K99/R00MH081058 / MH / NIMH NIH HHS / United States
R21 MH086128 / MH / NIMH NIH HHS / United States
R00 MH081058 / MH / NIMH NIH HHS / United States
NS056306 / NS / NINDS NIH HHS / United States
K99 MH081058 / MH / NIMH NIH HHS / United States
MH086128 / MH / NIMH NIH HHS / United States