{"doi":"10.1101/2022.12.23.521801","title":"Membrane association is required for Stmn2-mediated axon protection","abstract":"ABSTRACT Axon integrity is essential for functional connectivity in the nervous system. The degeneration of stressed or damaged axons is a common and sometimes initiating event in neurodegenerative disorders. Cellular factors that preserve axon integrity have an important influence on the fate of a damaged axon. Stathmin-2 (Stmn2) is an axon maintenance factor that is depleted in Amyotrophic Lateral Sclerosis and replenishment of Stmn2 can restore neurite outgrowth in diseased neurons. Stathmins have a well-documented role in microtubule dynamics during neurodevelopment, yet mechanisms responsible for Stmn2-mediated axon maintenance in injured neurons are not known. We demonstrate that membrane association of Stmn2 is critical for its axon-protective activity. Axonal enrichment of Stmn2 is driven by palmitoylation as well as tubulin interaction. We discover that another Stathmin, Stmn3, co-migrates with Stmn2-containing vesicles and undergoes regulated degradation through DLK-JNK signaling. The Stmn2 membrane targeting domain is both necessary and sufficient for localization to a specific vesicle population and confers sensitivity to DLK-dependent degradation. Our findings reveal a broader role for DLK in tuning the local abundance of palmitoylated Stathmins in axon segments. Moreover, palmitoylation is a critical component of Stathmin-mediated axon protection and defining the Stmn2-containing vesicle population will provide important clues toward mechanisms of axon maintenance.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":305122,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":999032,"name":"Jerianne E. Richardson","orcid":null,"position":1,"is_corresponding":false},{"id":593348,"name":"Daniel W. Summers","orcid":"0000-0001-7228-8849","position":2,"is_corresponding":false},{"id":998613,"name":"Emma J. C. Thornburg‐Suresh","orcid":"0000-0002-2773-8158","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:37.185846Z","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":[]}