{"doi":"10.1085/jgp.202413604","title":"Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle","abstract":"Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere \"C-zone,\" MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal that MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development and prompting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility in the C-zone? Globular domains critical to MyBP-C's modulatory functions are absent from MyBP-H, suggesting that MyBP-H may be functionally silent. However, our results suggest an active role. In vitro motility experiments indicate MyBP-H shares MyBP-C's capacity as a molecular \"brake.\" These results provide new insights and raise questions about the role of the C-zone during muscle development.","journal":"The Journal of General Physiology","year":2024,"id":449351,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":774934,"name":"Neil B. Wood","orcid":"0000-0001-6352-6358","position":1,"is_corresponding":false},{"id":347182,"name":"Shane R. Nelson","orcid":"0000-0002-3032-6314","position":2,"is_corresponding":false},{"id":369666,"name":"Bradley M. Palmer","orcid":"0000-0002-4388-3160","position":3,"is_corresponding":false},{"id":298738,"name":"Lin Yang","orcid":"0000-0003-1057-9194","position":4,"is_corresponding":false},{"id":347183,"name":"Samantha Beck Previs","orcid":"0000-0002-5516-1579","position":5,"is_corresponding":false},{"id":1269112,"name":"Angela Ploysangngam","orcid":null,"position":6,"is_corresponding":false},{"id":349246,"name":"Guy G. Kennedy","orcid":null,"position":7,"is_corresponding":false},{"id":555400,"name":"Jennifer McAdow","orcid":"0000-0003-0898-4879","position":8,"is_corresponding":false},{"id":895226,"name":"Sarah M. Tremble","orcid":"0000-0002-2153-2714","position":9,"is_corresponding":false},{"id":1269113,"name":"Marcus A. Zimmermann","orcid":null,"position":10,"is_corresponding":false},{"id":366316,"name":"Marilyn J. Cipolla","orcid":"0000-0002-9172-5941","position":11,"is_corresponding":false},{"id":369667,"name":"Alicia M. Ebert","orcid":"0000-0002-1112-2009","position":12,"is_corresponding":false},{"id":555403,"name":"Aaron N. Johnson","orcid":"0000-0002-2783-5636","position":13,"is_corresponding":false},{"id":247594,"name":"Christina A. Gurnett","orcid":"0000-0001-9129-315X","position":14,"is_corresponding":false},{"id":457219,"name":"Michael J. Previs","orcid":"0000-0002-8851-7439","position":15,"is_corresponding":false},{"id":347184,"name":"David M. Warshaw","orcid":"0000-0002-0071-8798","position":16,"is_corresponding":false},{"id":369665,"name":"Andrew F. Mead","orcid":"0000-0003-4716-2149","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:02:16.291892Z","pmid":"39373654","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":[]}