{"doi":"10.1530/rep-25-0114","title":"Na+,K+-ATPase α isoforms in sperm show a highly structured and distinct pattern of distribution","abstract":"In brief: This manuscript shows that the Na+ and K+ transporter Na+,K+-ATPase α4, specific to sperm, is expressed on the surface of the sperm head and flagellum in a very structured manner. This is also true for Na+,K+-ATPase α1, the other Na+,K+-ATPase isoform present in sperm and also in all cells. However, Na+,K+-ATPase α4 distribution changes when the cells are capacitated, an event necessary for fertilization. This dynamic remodeling, along with the distinct functional properties of Na+,K+-ATPase α4 and α1, provides evidence for the refined level of specialization that sperm have developed to achieve the amazing goal of fertilizing the oocyte. Abstract: Na+,K+-ATPase α4 is a unique Na+ and K+ transporter of the plasma membrane of spermatozoa, which is essential for male fertility. While previous studies have found Na+,K+-ATPase α4 to be mainly expressed in the sperm flagellum, less is known about its localization in the sperm head. Moreover, the spatial arrangement of Na+,K+-ATPase α4 at the subcellular level and its relationship to the functional state of the cells are unclear. We studied this using stimulated emission depletion (STED) super-resolution microscopy. We show that, under non-capacitated conditions, Na+,K+-ATPase α4 is distributed in a trilinear pattern along the midpiece and as a scattered single line along the principal piece of the sperm flagellum. Under capacitated conditions, Na+,K+-ATPase α4 pattern undergoes remodeling and its distribution shifts to a single line along the flagellum. On the other hand, Na+,K+-ATPase α1, the somatic isoform of Na+,K+-ATPase also present in sperm, exhibits a similar trilaminar localization at the flagellar midpiece but a bilinear pattern in the principal piece. This distribution, unlike that of Na+,K+-ATPase α4, does not change during sperm capacitation. We also found Na+,K+-ATPase α1 and α4 in the sperm head, where they present a complex distribution under both non-capacitated and capacitated conditions. These differences in the localization pattern and spatial dynamics of Na+,K+-ATPase isoform expression, along with their different functional properties, highlight the distinct roles that both isoforms play to support sperm function.","journal":"Reproduction","year":2025,"id":523920,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1269364,"name":"Jeffrey P. McDermott","orcid":"0000-0002-3566-3483","position":1,"is_corresponding":false},{"id":731606,"name":"Gladis Sánchez","orcid":"0000-0003-1023-7290","position":2,"is_corresponding":false},{"id":731605,"name":"Gustavo Blanco","orcid":"0000-0001-7721-9869","position":3,"is_corresponding":false},{"id":1293950,"name":"Mumtarin Jannat Oishee","orcid":"0000-0001-5101-9930","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:50:07.396155Z","pmid":"40762410","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":[]}