{"doi":"10.1101/2022.05.13.491857","title":"Arf GTPase activates the WAVE Regulatory Complex through a novel binding site","abstract":"Summary Crosstalk between Rho- and Arf-family GTPases plays an important role in linking actin cytoskeletal remodeling to membrane protrusion, organelle structure, and vesicle trafficking. The central actin regulator, WAVE Regulatory Complex (WRC), is a converging point of Rac1 (a Rho-family GTPase) and Arf signaling in many processes, but how Arf promotes WRC activation is unknown. Here we reconstituted a direct interaction between Arf and WRC. This interaction can be greatly enhanced by Rac1 binding to the D site of the WRC. Arf1 binds to a newly identified conserved surface on Sra1 located between the D site and the WH2 helix of WAVE1, which can drive WRC activation using a mechanism distinct from that of Rac1. Mutating Arf binding site abolishes Arf1-WRC interaction, disrupts Arf1-mediated WRC activation, and impairs lamellipodia morphology. This work uncovers a new mechanism underlying WRC activation and provides a mechanistic foundation for studying how WRC-mediated actin polymerization links Arf and Rac signaling in the cell.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":308637,"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":0.9601,"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":854704,"name":"Yijun Liu","orcid":"0009-0000-5612-7666","position":1,"is_corresponding":false},{"id":855475,"name":"Abbigale J. Brown","orcid":null,"position":2,"is_corresponding":false},{"id":473930,"name":"Matthias Schaks","orcid":"0000-0001-6362-7909","position":3,"is_corresponding":false},{"id":854703,"name":"Bojian Ding","orcid":"0000-0002-6648-3477","position":4,"is_corresponding":false},{"id":709098,"name":"Daniel A. Kramer","orcid":"0000-0002-7159-9562","position":5,"is_corresponding":false},{"id":612115,"name":"Ding Li","orcid":"0000-0002-3581-7630","position":6,"is_corresponding":false},{"id":1003451,"name":"Olga Alekhina","orcid":"0000-0002-2738-5399","position":7,"is_corresponding":false},{"id":290939,"name":"Daniel D. Billadeau","orcid":"0000-0002-2296-9547","position":8,"is_corresponding":false},{"id":314359,"name":"Saikat Chowdhury","orcid":"0000-0001-8043-5028","position":9,"is_corresponding":false},{"id":86256,"name":"Junmei Wang","orcid":"0000-0002-9607-8229","position":10,"is_corresponding":false},{"id":473932,"name":"Klemens Rottner","orcid":"0000-0003-4244-4198","position":11,"is_corresponding":false},{"id":281969,"name":"Baoyu Chen","orcid":"0000-0002-6366-159X","position":12,"is_corresponding":false},{"id":281958,"name":"Sheng Yang","orcid":"0000-0002-0321-3728","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T00:33:07.132912Z","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":[]}