{"doi":"10.3389/fncel.2020.573345","title":"Caspase-3 Cleaves Extracellular Vesicle Proteins During Auditory Brainstem Development","abstract":"Sound localization requires extremely precise development of auditory brainstem circuits, the molecular mechanisms of which are largely unknown. We previously demonstrated a novel requirement for non-apoptotic activity of the protease caspase-3 in chick auditory brainstem development. Here, we used mass spectrometry to identify proteolytic substrates of caspase-3 during chick auditory brainstem development. These auditory brainstem caspase-3 substrates were enriched for proteins previously shown to be cleaved by caspase-3, especially in non-apoptotic contexts. Functional annotation analysis revealed that our caspase-3 substrates were also enriched for proteins associated with several protein categories, including proteins found in extracellular vesicles (EVs), membrane-bound nanoparticles that function in intercellular communication. The proteome of EVs isolated from the auditory brainstem was highly enriched for our caspase-3 substrates. Additionally, we identified two caspase-3 substrates with known functions in axon guidance, namely Neural Cell Adhesion Molecule (NCAM) and Neuronal-glial Cell Adhesion Molecule (Ng-CAM), that were found in auditory brainstem EVs and expressed in the auditory pathway alongside cleaved caspase-3. Taken together, these data suggest a novel developmental mechanism whereby caspase-3 influences auditory brainstem circuit formation through the proteolytic cleavage of extracellular vesicle (EV) proteins.","journal":"Frontiers in Cellular Neuroscience","year":2020,"id":79855,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":414377,"name":"Yeva Mirzakhanyan","orcid":"0000-0002-4276-8937","position":1,"is_corresponding":false},{"id":415103,"name":"Kian J. Samimi","orcid":null,"position":2,"is_corresponding":false},{"id":415104,"name":"Mehron Dhillon","orcid":null,"position":3,"is_corresponding":false},{"id":277234,"name":"Melanie Barzik","orcid":"0000-0003-3003-1281","position":4,"is_corresponding":false},{"id":277239,"name":"Lisa L. Cunningham","orcid":"0000-0001-5320-964X","position":5,"is_corresponding":false},{"id":414378,"name":"Paul D. Gershon","orcid":"0000-0002-4904-9193","position":6,"is_corresponding":false},{"id":414379,"name":"Karina S. Cramer","orcid":"0000-0003-3793-4862","position":7,"is_corresponding":false},{"id":414376,"name":"Forrest Weghorst","orcid":"0000-0001-9365-1846","position":0,"is_corresponding":true}],"reference_count":163,"raw_metadata":null,"created_at":"2026-07-18T21:50:57.971597Z","pmid":"33281555","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}