{"doi":"10.1242/jcs.122184","title":"Direct binding of TUBB3 with DCC couples netrin-1 signaling to intracellular microtubule dynamics in axon outgrowth and guidance","abstract":"<jats:p>The coupling of axon guidance cues, such as netrin-1, to microtubule (MT) dynamics is essential for growth cone navigation in the developing nervous system. However, whether axon guidance signaling regulates MT dynamics directly or indirectly is unclear. Here, we report that TUBB3, the most dynamic β–tubulin isoform in neurons, directly interacts with the netrin receptor DCC, and that netrin-1 induces this interaction in primary neurons. TUBB3 colocalizes with DCC in the growth cones of primary neurons and MT dynamics is required for netrin-1-promoted association of TUBB3 with DCC. Netrin-1 not only increases cosedimentation of DCC with polymerized MT, but also promotes MT dynamics in the growth cone. Knocking down TUBB3 inhibits netrin-1-induced MT dynamics, axon outgrowth and attraction in vitro and causes defects in commissural axon projection in the embryo. These results indicate that TUBB3 directly links netrin signaling pathways to MT dynamics and plays an important role in guiding commissural axons in vivo.</jats:p>","journal":"Journal of Cell Science","year":2013,"id":57474,"datarank":2.3016410290637808,"base_score":4.07753744390572,"endowment":4.07753744390572,"self_citation_contribution":0.611630616585858,"citation_network_contribution":1.6900104124779227,"self_endowment_contribution":0.611630616585858,"citer_contribution":1.6900104124779227,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":51,"citers_with_citation_signal":46,"citers_with_endowment":46,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":300618,"name":"Trisha Dwyer","orcid":null,"position":1,"is_corresponding":false},{"id":300619,"name":"Qiangqiang Shao","orcid":null,"position":2,"is_corresponding":false},{"id":158633,"name":"Tao Yang","orcid":null,"position":3,"is_corresponding":false},{"id":300620,"name":"Huai Huang","orcid":null,"position":4,"is_corresponding":false},{"id":300621,"name":"Guofa Liu","orcid":null,"position":5,"is_corresponding":false},{"id":300617,"name":"Chao Qu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Direct binding of TUBB3 with DCC couples netrin-1 signaling to intracellular microtubule dynamics in axon outgrowth and guidance","abstract":"<jats:p>The coupling of axon guidance cues, such as netrin-1, to microtubule (MT) dynamics is essential for growth cone navigation in the developing nervous system. However, whether axon guidance signaling regulates MT dynamics directly or indirectly is unclear. Here, we report that TUBB3, the most dynamic β–tubulin isoform in neurons, directly interacts with the netrin receptor DCC, and that netrin-1 induces this interaction in primary neurons. TUBB3 colocalizes with DCC in the growth cones of primary neurons and MT dynamics is required for netrin-1-promoted association of TUBB3 with DCC. Netrin-1 not only increases cosedimentation of DCC with polymerized MT, but also promotes MT dynamics in the growth cone. Knocking down TUBB3 inhibits netrin-1-induced MT dynamics, axon outgrowth and attraction in vitro and causes defects in commissural axon projection in the embryo. These results indicate that TUBB3 directly links netrin signaling pathways to MT dynamics and plays an important role in guiding commissural axons in vivo.</jats:p>","is_dataset_classified":null,"base_score":4.07753744390572,"endowment":4.07753744390572,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23641072","pmcid":"PMC3711200","openalex_id":"https://openalex.org/W2008963615","authors":[],"funders":[{"funder_name":"NICHD NIH HHS","grant_id":"R15 HD080512","title":null}],"total_grants":1,"fwci":2.6252,"citation_percentile":0.89380531,"influential_citations":0,"citation_trend":[{"year":2013,"count":1},{"year":2014,"count":5},{"year":2015,"count":7},{"year":2016,"count":6},{"year":2017,"count":8},{"year":2018,"count":5},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":6},{"year":2022,"count":5},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":4}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1242/jcs.122184","host_type":"journal"},{"url":"https://doi.org/10.1242/jcs.122184","host_type":"HYBRID"},{"url":"https://doi.org/10.1242/jcs.122184","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/126/14/3070/1931779/jcs-126-14-3070.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.122184/2045008/jcs122184.pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23641072","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3711200","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3711200","host_type":"repository"}],"fields_of_study":["Axon Guidance and Neuronal Signaling","Neurogenesis and neuroplasticity mechanisms","Hippo pathway signaling and YAP/TAZ","Biology","Medicine","Animals","Axons","Cell Growth Processes","Chick Embryo","DCC Receptor","Gene Knockdown Techniques","HEK293 Cells","Humans","Intracellular Space","Mice","Microtubules","Nerve Growth Factors","Netrin-1","Neurons","Protein Binding","Protein Transport","RNA, Small Interfering","Receptors, Cell Surface","Signal Transduction","Spinal Cord","Transgenes","Tubulin","Tumor Suppressor Proteins"],"mesh_terms":["Netrin-1","DCC Receptor","Animals","Axons","Chick Embryo","Humans","Microtubules","Nerve Growth Factors","Neurons","Protein Binding","Receptors, Cell Surface","Spinal Cord","Tubulin","Signal Transduction","Transgenes","Protein Transport","Tumor Suppressor Proteins","RNA, Small Interfering","Intracellular Space","Cell Growth Processes","Mice","Gene Knockdown Techniques","HEK293 Cells"],"keywords":["Netrin","Axon guidance","Biology","Growth cone","Axon","Deleted in Colorectal Cancer","Neuroscience","Microtubule","Floor plate","Cell biology","Commissure","Genetics","Signal transduction","DCC","Microtubule Dynamics","Tubb3"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-18T21:06:43.394751Z","pmid":null,"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":[]}