{"doi":"10.1101/2022.10.28.514228","title":"Palmitoylation regulates neuropilin-2 localization and function in cortical neurons and conveys specificity to semaphorin signaling via palmitoyl acyltransferases","abstract":"ABSTRACT Secreted semaphorin 3F (Sema3F) and semaphorin 3A (Sema3A) exhibit remarkably distinct effects on deep layer excitatory cortical pyramidal neurons; Sema3F mediates dendritic spine pruning, whereas Sema3A promotes the elaboration of basal dendrites. Sema3F and Sema3A signal through distinct holoreceptors that include neuropilin-2 (Nrp-2)/plexinA3 (PlexA3) and neuropilin-1 (Nrp-1)/PlexA4, respectively. We find that Nrp-2 and Nrp-1 are S-palmitoylated in cortical neurons and that palmitoylation of select Nrp-2 cysteines is required for its proper subcellular localization and also for Sema3F/Nrp-2-dependent dendritic spine pruning in cortical neurons, both in vitro and in vivo. Moreover, we show that the palmitoyl acyltransferase DHHC15 is required for Nrp-2 palmitoylation and Sema3F/Nrp-2-dependent dendritic spine pruning, but it is dispensable for Nrp-1 palmitoylation and Sema3A/Nrp-1-dependent basal dendritic elaboration. Therefore, palmitoyl acyltransferase-substrate specificity is essential for establishing compartmentalized neuronal structure and functional responses to extrinsic guidance cues. HIGHLIGHTS Neuropilins (Nrps) are S-palmitoylated in vitro and in vivo in the central nervous system S-palmitoylation of select Nrp-2 cysteines confers subcellular localization specificity and is required for semaphorin 3F-dependent dendritic spine pruning in cortical neurons Distinct palmitoyl acyltransferases mediate Nrp-2 and Nrp-1 palmitoylation and function, imparting specificity to semaphorin signaling","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":312953,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"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":1010787,"name":"Qiang Wang","orcid":"0000-0002-7159-4446","position":1,"is_corresponding":false},{"id":707878,"name":"Rebeca Mejı́as","orcid":"0000-0003-1936-7219","position":2,"is_corresponding":false},{"id":836208,"name":"Randal Hand","orcid":null,"position":3,"is_corresponding":false},{"id":707883,"name":"Tao Wang","orcid":"0000-0002-9697-4082","position":4,"is_corresponding":false},{"id":225743,"name":"David D. Ginty","orcid":"0000-0001-9723-8530","position":5,"is_corresponding":false},{"id":337480,"name":"Alex L. Kolodkin","orcid":"0000-0001-7562-5513","position":6,"is_corresponding":false},{"id":1010786,"name":"Eleftheria Koropouli","orcid":"0000-0001-8537-4471","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T00:33:40.460845Z","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":[]}