{"doi":"10.3389/fcell.2020.572735","title":"Molecular Mechanism Underlying the Action of Zona-pellucida Glycoproteins on Mouse Sperm","abstract":"Mammalian oocytes are enveloped by the zona pellucida (ZP), an extracellular matrix of glycoproteins. In sperm, stimulation with ZP proteins evokes a rapid Ca2+ influx via the sperm-specific, pH-sensitive Ca2+ channel CatSper. However, the physiological role and molecular mechanisms underlying ZP-dependent activation of CatSper are unknown. Here, we delineate the sequence of ZP-signaling events in mouse sperm. We show that ZP proteins evoke a rapid intracellular pHi increase that rests predominantly on Na+/H+ exchange by NHA1 and requires cAMP synthesis by the soluble adenylyl cyclase sAC as well as a hyperpolarized membrane potential set by the spem-specific K+ channel Slo3. The alkaline-activated CatSper channel translates the ZP-induced pHi increase into a Ca2+ response. Our findings reveal the molecular components underlying ZP action on mouse sperm, opening up new avenues for understanding the basic principles of sperm function and, thereby, mammalian fertilization.","journal":"Frontiers in Cell and Developmental Biology","year":2020,"id":97298,"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":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":481282,"name":"Hussein Hamzeh","orcid":"0000-0002-3056-788X","position":1,"is_corresponding":false},{"id":482124,"name":"Jan F. Jikeli","orcid":null,"position":2,"is_corresponding":false},{"id":481283,"name":"Christoph Brenker","orcid":"0000-0002-4230-2571","position":3,"is_corresponding":false},{"id":481284,"name":"Christian Schiffer","orcid":"0000-0002-2544-843X","position":4,"is_corresponding":false},{"id":481285,"name":"Jan N. Hansen","orcid":"0000-0002-0489-7535","position":5,"is_corresponding":false},{"id":482125,"name":"Pia Neugebauer","orcid":null,"position":6,"is_corresponding":false},{"id":482126,"name":"Christian Trötschel","orcid":null,"position":7,"is_corresponding":false},{"id":481286,"name":"Luca Jovine","orcid":"0000-0002-2679-6946","position":8,"is_corresponding":false},{"id":481287,"name":"Ling Han","orcid":"0000-0001-9310-4789","position":9,"is_corresponding":false},{"id":481288,"name":"Harvey M. Florman","orcid":"0000-0002-2399-3493","position":10,"is_corresponding":false},{"id":481289,"name":"U. Benjamin Kaupp","orcid":"0000-0002-0696-6397","position":11,"is_corresponding":false},{"id":282593,"name":"Timo Strünker","orcid":"0000-0003-0812-1547","position":12,"is_corresponding":false},{"id":481290,"name":"Dagmar Wachten","orcid":"0000-0003-4800-6332","position":13,"is_corresponding":false},{"id":456905,"name":"Melanie Balbach","orcid":"0000-0002-9752-9888","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T22:35:34.520494Z","pmid":"32984353","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":[]}