{"doi":"10.1101/2023.02.27.530328","title":"Syndapin Regulates the RAP-1 GTPase to Control Endocytic Recycling via RHO-1 and Non-Muscle Myosin II","abstract":"Abstract After endocytosis, many plasma membrane components are recycled via narrow-diameter membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that the F-BAR and SH3 domain Syndapin/PACSIN-family protein SDPN-1 is required in vivo for basolateral endocytic recycling in the C. elegans intestine. Here we sought to determine the significance of a predicted interaction between the SDPN-1 SH3 domain and a target sequence in PXF-1/PDZ-GEF1/RAPGEF2, a known exchange factor for Rap-GTPases. We found that endogenous mutations we engineered into the SDPN-1 SH3 domain, or its binding site in the PXF-1 protein, interfere with recycling in vivo , as does loss of the PXF-1 target RAP-1. Rap-GTPases have been shown in several contexts to negatively regulate RhoA activity. Our results show that RHO-1/RhoA is enriched on SDPN-1 and RAP-1 positive endosomes in the C. elegans intestine, and loss of SDPN-1 or RAP-1 elevates RHO-1(GTP) levels on intestinal endosomes. Furthermore, we found that depletion of RHO-1 suppressed sdpn-1 mutant recycling defects, indicating that control of RHO-1 activity is a key mechanism by which SDPN-1 acts to promote endocytic recycling. RHO-1/RhoA is well-known for controlling actomyosin contraction cycles, although little is known of non-muscle myosin II on endosomes. Our analysis found that non-muscle myosin II is enriched on SDPN-1 positive endosomes, with two non-muscle myosin II heavy chain isoforms acting in apparent opposition. Depletion of nmy-2 inhibited recycling like sdpn-1 mutants, while depletion of nmy-1 suppressed sdpn-1 mutant recycling defects, indicating actomyosin contractility in controlling recycling endosome function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":403364,"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":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":304337,"name":"Anne Norris","orcid":"0000-0003-3797-7416","position":1,"is_corresponding":false},{"id":1138656,"name":"Agustin B. Velasco","orcid":null,"position":2,"is_corresponding":false},{"id":674791,"name":"Adenrele M. Gleason","orcid":null,"position":3,"is_corresponding":false},{"id":304338,"name":"Barth D. Grant","orcid":"0000-0002-5943-8336","position":4,"is_corresponding":false},{"id":1138655,"name":"Wilmer R. Rodriguez-Polanco","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:36.280647Z","pmid":"36909525","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":[]}