title: Coupled local translation and degradation regulate growth cone collapse.
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.
authors.affiliation: 1] Graduate Program in Neuroscience, Weill Cornell Graduate School of Medical Sciences of Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Department of Pharmacology, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Alessia
authors.identifier: 0000000305647746
authors.initials: A
authors.lastname: Deglincerti
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Yaobin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.affiliation: Department of Pharmacology, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hengst
authors.affiliation: 1] Department of Pharmacology, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.affiliation: 1] Graduate Program in Neuroscience, Weill Cornell Graduate School of Medical Sciences of Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Department of Pharmacology, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Samie R
authors.initials: SR
authors.lastname: Jaffrey
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D018274:Electroporation; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D040121:Semaphorin-3A / Q000494:pharmacology; D013116:Spinal Cord; D044767:Ubiquitin-Protein Ligases / Q000187:drug effects / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D040121:Semaphorin-3A; D020932:Nerve Growth Factor; C492381:Smurf1 protein, mouse; C556581:Smurf1 protein, rat; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D020742:rhoA GTP-Binding Protein