{"doi":"10.1101/2024.12.31.630845","title":"BORC segregates synaptic vesicle and lysosomal proteins through motors UNC-104/KIF1A and UNC-116/KIF5","abstract":"Abstract While synaptic vesicle proteins (SVPs) and lysosomal proteins can be present together in axons, the origin of these compartments is unclear. These SV-lysosomes are however thought to segregate further to SVPs and lysosomal proteins. In this study, we identify genes and characterize a genetic pathway involved in the segregation of SVPs and lysosomal proteins in the neuronal cell body. We identify a novel role for BORC (BLOC-1-related complex) in segregating SVPs and lysosomal proteins in the cell body. BORC subunit SAM-4/Myrlysin acts through ARL-8 and Kinesin motor proteins UNC-116/KIF5 and UNC-104/KIF1A in segregating SVPs and lysosomal proteins. Additionally, we also show that LRK-1/LRRK2 and APB-3/AP-3 (β3), involved in pre-SV biogenesis, regulate the segregation of SVPs and lysosomal proteins in the neuronal cell body. LRK-1 recruits SAM-4 that in turn governs the localisation of APB-3 suggesting a hierarchical pathway of LRK-1-SAM-4-APB-3 for the segregation of SVPs and lysosomal proteins. Additionally, we also observe that the size of lysosomal protein-containing compartments (LPCCs) is smaller in SAM-4 and LRK-1. This size regulation depends on UNC-116. Together, we show that BORC recruited by LRK-1 and in turn via motors and along with AP-3 mediates the segregation of SVPs and lysosomal proteins in the neuronal cell body.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556971,"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":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1456655,"name":"Sohan Seal","orcid":"0000-0001-5191-6877","position":1,"is_corresponding":false},{"id":1457136,"name":"Aditee Dandekar","orcid":null,"position":2,"is_corresponding":false},{"id":1457137,"name":"Badal Singh Chauhan","orcid":null,"position":3,"is_corresponding":false},{"id":1457138,"name":"Sruthi Sivadasan","orcid":null,"position":4,"is_corresponding":false},{"id":287301,"name":"Michael L. Nonet","orcid":null,"position":5,"is_corresponding":false},{"id":486106,"name":"Sandhya P. Koushika","orcid":"0000-0002-1742-7356","position":6,"is_corresponding":false},{"id":1456654,"name":"Amal Mathew","orcid":"0000-0003-1466-4863","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:13.130091Z","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":[]}