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.
Source: Nature Communications
DOI: 10.1038/ncomms7888
Institutions: Cornell University, Weill Cornell Medicine, Soochow University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Natural Science Foundation of China, Priority Academic Program Development of Jiangsu Higher Education Institutions, National Institutes of Health, University of California, Irvine, Qatar National Research Fund, National Key Research and Development Program of China, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke
Awards: G1036770068, G1675797667, G1785284928, G1828425977, Mechanisms of Axonal Pathfinding Controlled by Netrin-1, G3282608986, G3699247576, Intra-axonal signaling pathways triggered by attractive guidance cues., G4664741995, Comprehensive profiling of ubiquitination in neurons, Mechanisms of Axonal Pathfinding Controlled by Netrin-1, 来那度胺治疗多发性骨髓瘤的分子机制研究, G6645283138, G9000123529
OpenAlex ID: W2072977612
