{"doi":"10.1016/j.jmb.2023.168421","title":"Drebrin Protects Assembled Actin from INF2-FFC-mediated Severing and Stabilizes Cell Protrusions","abstract":"• DrebrinA decorates actin filaments and protects them from their INF2-mediated severing/disassembly. • Structural changes in actin filaments due to drebrinA binding potentially inhibit their severing/disassembly by INF2. • DrebrinA and INF2 are abundantly expressed in neurons and podocytes. • Their strategic presence and antagonistic activity in cells may help in determining the state of actin filaments, especially at the tip and base of filopodia-like protrusions. Highly specialized cells, such as neurons and podocytes, have arborized morphologies that serve their specific functions. Actin cytoskeleton and its associated proteins are responsible for the distinctive shapes of cells. The mechanism of their cytoskeleton regulation – contributing to cell shape maintenance – is yet to be fully clarified. Inverted formin 2 (INF2), one of the modulators of the cytoskeleton, is an atypical formin that can both polymerize and depolymerize actin filaments depending on its molar ratio to actin. Prior work has established that INF2 binds to the sides of actin filaments and severs them. Drebrin is another actin-binding protein that also binds filaments laterally and stabilizes them, but the interplay between drebrin and INF2 on actin filament stabilization is not well understood. Here, we have used biochemical assays, electron microscopy, and total internal reflection fluorescence microscopy imaging to show that drebrin protects actin filaments from severing by INF2 without inhibiting its polymerization activity. Notably, truncated drebrin – DrbA1-300 – is sufficient for this protection, though not as effective as the full-length protein. INF2 and drebrin are abundantly expressed in highly specialized cells and are crucial for the temporal regulation of their actin cytoskeleton, consistent with their involvement in peripheral neuropathy.","journal":"Journal of Molecular Biology","year":2023,"id":379436,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"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":1143833,"name":"Roman Aguirre","orcid":"0009-0007-2339-8268","position":1,"is_corresponding":false},{"id":266761,"name":"Z. Hong Zhou","orcid":"0000-0002-8373-4717","position":2,"is_corresponding":false},{"id":1143834,"name":"Péter Hauser","orcid":"0000-0003-1168-034X","position":3,"is_corresponding":false},{"id":329147,"name":"Emil Reisler","orcid":"0000-0001-7705-7791","position":4,"is_corresponding":false},{"id":1002362,"name":"Sudeepa Rajan","orcid":"0000-0002-1455-2426","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T01:16:52.622552Z","pmid":"38158176","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":[]}