{"doi":"10.1073/pnas.2309955120","title":"Disassembly of bundled F-actin and cellular remodeling via an interplay of Mical, cofilin, and F-actin crosslinkers","abstract":"Cellular form and function are controlled by the assembly and stability of actin cytoskeletal structures-but disassembling/pruning these structures is equally essential for the plasticity and remodeling that underlie behavioral adaptations. Importantly, the mechanisms of actin assembly have been well-defined-including that it is driven by actin's polymerization into filaments (F-actin) and then often bundling by crosslinking proteins into stable higher-order structures. In contrast, it remains less clear how these stable bundled F-actin structures are rapidly disassembled. We now uncover mechanisms that rapidly and extensively disassemble bundled F-actin. Using biochemical, structural, and imaging assays with purified proteins, we show that F-actin bundled with one of the most prominent crosslinkers, fascin, is extensively disassembled by Mical, the F-actin disassembly enzyme. Furthermore, the product of this Mical effect, Mical-oxidized actin, is poorly bundled by fascin, thereby further amplifying Mical's disassembly effects on bundled F-actin. Moreover, another critical F-actin regulator, cofilin, also affects fascin-bundled filaments, but we find herein that it synergizes with Mical to dramatically amplify its disassembly of bundled F-actin compared to the sum of their individual effects. Genetic and high-resolution cellular assays reveal that Mical also counteracts crosslinking proteins/bundled F-actin in vivo to control cellular extension, axon guidance, and Semaphorin/Plexin cell-cell repulsion. Yet, our results also support the idea that fascin-bundling serves to dampen Mical's F-actin disassembly in vitro and in vivo-and that physiologically relevant cellular remodeling requires a fine-tuned interplay between the factors that build bundled F-actin networks and those that disassemble them.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":337624,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"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":792786,"name":"Jimok Yoon","orcid":null,"position":1,"is_corresponding":false},{"id":685322,"name":"Heng Wu","orcid":"0000-0002-7161-7281","position":2,"is_corresponding":false},{"id":1070056,"name":"Sargis Srapyan","orcid":null,"position":3,"is_corresponding":false},{"id":692628,"name":"Raju Baskar","orcid":"0000-0003-2450-0598","position":4,"is_corresponding":false},{"id":685321,"name":"Giasuddin Ahmed","orcid":"0000-0002-4730-2925","position":5,"is_corresponding":false},{"id":844107,"name":"Taehong Yang","orcid":"0000-0001-6392-5631","position":6,"is_corresponding":false},{"id":329146,"name":"Elena E. Grintsevich","orcid":"0000-0002-9671-6139","position":7,"is_corresponding":false},{"id":329147,"name":"Emil Reisler","orcid":"0000-0001-7705-7791","position":8,"is_corresponding":false},{"id":685324,"name":"Jonathan R. Terman","orcid":"0000-0002-9898-8293","position":9,"is_corresponding":false},{"id":1002362,"name":"Sudeepa Rajan","orcid":"0000-0002-1455-2426","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:10:31.133446Z","pmid":"37725655","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":[]}