Work

Coupled local translation and degradation regulate growth cone collapse

Year: 2015
Type: article
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. Local protein translation regulates growth cone dynamics in response to guidance cues. Here the authors show that locally translated proteins are the main targets of the ubiquitin-proteasome system, and that local signalling promotes the ubiquitination and degradation of RhoA, leading to growth cone collapse.
Language: English
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2072977612
FWCI: 3.026
Cites: 50
Cited by: 55
Related to: 10