{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:07:57Z","timestamp":1792843677515,"version":"4.5.0"},"reference-count":49,"publisher":"The Company of Biologists","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>To reside in marine habitats, marine fishes must actively eliminate the excess Na+ and Cl\u2212 they acquire from their environment. These ions are passively absorbed across body surfaces and through the ingestion of seawater (SW), which is necessary to maintain water balance. Salt secretion occurs through the actions of mitochondrion-rich \u2018SW-type ionocytes\u2019 in the gills or other specialized salt-secreting organs. For nearly 50\u2005years, the SW-type ionocyte model proposed by Patricio Silva and colleagues has proven remarkably enduring. The Silva model guided researchers toward identifying key molecular components of SW-type ionocytes, such as cystic fibrosis transmembrane conductance regulator 1 (Cftr1), Na+\/K+\/2Cl\u2212 cotransporter 1 (Nkcc1) and the inwardly rectifying K+ channel (Kir). However, emerging findings indicate that alternative molecular mechanisms may complement, or in some cases, operate in lieu of those included in the Silva model. In this Commentary, we argue that it is time to critically evaluate whether ionocyte-based strategies for salt secretion are more diverse than currently recognized. We highlight recent developments regarding the operation of Cftr-independent ionocytes in lamprey, the emerging role of anoctamin 1 (Ano1) in lamprey and bony fishes, and various \u2018new\u2019 pathways for Cl\u2212 and K+ to enter and exit ionocytes. Additionally, we propose future research directions for identifying novel salt-secretory mechanisms in various lineages of marine fishes. We conclude this Commentary by presenting three hypotheses for the divergence of ionocyte-mediated salt secretion in marine fishes and outlining a conceptual framework for considering the evolutionary homology of salt-secreting ionocytes across vertebrates.<\/jats:p>","DOI":"10.1242\/jeb.251075","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:48:12Z","timestamp":1762764492000},"source":"Crossref","is-referenced-by-count":5,"title":["Salt-secreting ionocytes in marine fishes: new dimensions and evolutionary implications of a fundamental model"],"prefix":"10.1242","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2146-9126","authenticated-orcid":false,"given":"Ciaran A.","family":"Shaughnessy","sequence":"first","affiliation":[{"name":"Oklahoma State University 1 Department of Integrative Biology , , Stillwater, OK 74078,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1193-4389","authenticated-orcid":false,"given":"Jason P.","family":"Breves","sequence":"additional","affiliation":[{"name":"Skidmore College, Saratoga Springs 2 Department of Biology , , NY 12866,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"2025111003480569100_JEB251075C1","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/nrg.2016.127","article-title":"The origin and evolution of cell types","volume":"17","author":"Arendt","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"2025111003480569100_JEB251075C2","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1242\/jeb.01157","article-title":"Cellular composition and ultrastructure of the gill epithelium of larval and adult lampreys: Implications for osmoregulation in fresh and seawater","volume":"207","author":"Bartels","year":"2004","journal-title":"J. Exp. Biol."},{"key":"2025111003480569100_JEB251075C3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/0010-406X(61)90053-6","article-title":"Studies on Myxine glutinosa\u2014I. The chemical composition of the tissues","volume":"3","author":"Bellamy","year":"1961","journal-title":"Comp. Biochem. Physiol."},{"key":"2025111003480569100_JEB251075C4","doi-asserted-by":"publisher","first-page":"R479","DOI":"10.1152\/ajpregu.00188.2024","article-title":"Salinity and prolactin regulate anoctamin 1 in the model teleost, Fundulus heteroclitus","volume":"327","author":"Breves","year":"2024","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2025111003480569100_JEB251075C5","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.devcel.2019.09.017","article-title":"An ancient CFTR ortholog informs molecular evolution in ABC transporters","volume":"51","author":"Cui","year":"2019","journal-title":"Dev. Cell"},{"key":"2025111003480569100_JEB251075C6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.cbpa.2010.06.164","article-title":"The curious case of the chemical composition of hagfish tissues - 50 years on","volume":"157","author":"Currie","year":"2010","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"2025111003480569100_JEB251075C7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/jez.1402360104","article-title":"The role of K+ and Cl\u2212 conductances in chloride secretion by the opercular epithelium","volume":"236","author":"Degnan","year":"1985","journal-title":"J. Exp. Zool."},{"key":"2025111003480569100_JEB251075C8","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1113\/jphysiol.1977.sp011995","article-title":"Active chloride transport in the in vitro opercular skin of a teleost (Fundulus heteroclitus), a gill\u2013like epithelium rich in chloride cells","volume":"271","author":"Degnan","year":"1977","journal-title":"J. Physiol."},{"key":"2025111003480569100_JEB251075C9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1749-6632.1985.tb14864.x","article-title":"Na\u2013K\u2013Cl cotransport in chloride\u2013transporting epithelia","volume":"456","author":"Epstein","year":"1985","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025111003480569100_JEB251075C10","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/259241a0","article-title":"The presence of Na\u2013Na and Na\u2013K exchange in sodium extrusion by three species of fish","volume":"259","author":"Evans","year":"1976","journal-title":"Nature"},{"key":"2025111003480569100_JEB251075C11","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1242\/jeb.64.1.203","article-title":"Sodium extrusion by the sea-water-acclimated fiddler crab Uca pugilator: comparison with other marine crustacea and marine teleost fish","volume":"64","author":"Evans","year":"1976","journal-title":"J. Exp. Biol."},{"key":"2025111003480569100_JEB251075C12","doi-asserted-by":"publisher","first-page":"R568","DOI":"10.1152\/ajpregu.00628.2011","article-title":"Potassium excretion through ROMK potassium channel expressed in gill mitochondrion-rich cells of Mozambique tilapia","volume":"302","author":"Furukawa","year":"2012","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2025111003480569100_JEB251075C13","doi-asserted-by":"publisher","first-page":"R1303","DOI":"10.1152\/ajpregu.00071.2014","article-title":"Gene expression and cellular localization of ROMKs in the gills and kidney of Mozambique tilapia acclimated to fresh water with high potassium concentration","volume":"307","author":"Furukawa","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2025111003480569100_JEB251075C14","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1242\/jeb.151.1.279","article-title":"Salinity-induced changes in branchial Na+\/K+-ATPase activity and transepithelial potential difference in the brine shrimp Artemia salina","volume":"151","author":"Holliday","year":"1990","journal-title":"J. Exp. Biol."},{"key":"2025111003480569100_JEB251075C15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5047\/absm.2008.00101.0001","article-title":"Functional morphology of mitochondrion-rich cells in euryhaline and stenohaline teleosts","volume":"1","author":"Kaneko","year":"2008","journal-title":"Aqua-BioSci. Monogr."},{"key":"2025111003480569100_JEB251075C16","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1126\/science.831273","article-title":"Chloride transport across isolated opercular epithelium of killifish: a membrane rich in chloride cells","volume":"195","author":"Karnaky","year":"1977","journal-title":"Science"},{"key":"2025111003480569100_JEB251075C17","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/978-3-662-00989-5_25","article-title":"Chloride cells and salt glands","volume-title":"Biology of the Integument: 2 Vertebrates","author":"Komnick","year":"1986"},{"key":"2025111003480569100_JEB251075C18","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/jez.2894","article-title":"Regulation of branchial anoctamin 1 expression in freshwater- and seawater-acclimated Japanese medaka, Oryzias latipes","volume":"343","author":"Konno","year":"2024","journal-title":"J. Exp. Zool. A Ecol. Integr. Physiol."},{"key":"2025111003480569100_JEB251075C19","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s00360-024-01560-6","article-title":"Cellular mechanisms of ion and acid-base regulation in teleost gill ionocytes","volume":"194","author":"Kovac","year":"2024","journal-title":"J. Comp. Physiol. B"},{"key":"2025111003480569100_JEB251075C20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-016-0001-8","article-title":"Salt secretion is linked to acid-base regulation of ionocytes in seawater-acclimated medaka: New insights into the salt-secreting mechanism","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"2025111003480569100_JEB251075C21","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.aquaculture.2018.03.032","article-title":"BK potassium channel mRNA level changes in gills of Atlantic salmon after brackish water transfer","volume":"491","author":"Loncoman","year":"2018","journal-title":"Aquaculture"},{"key":"2025111003480569100_JEB251075C22","doi-asserted-by":"publisher","first-page":"25438","DOI":"10.1016\/S0021-9258(19)74060-5","article-title":"The Na-K-Cl cotransport protein of shark rectal gland. II. Regulation by direct phosphorylation","volume":"267","author":"Lytle","year":"1992","journal-title":"J. Biol. Chem."},{"key":"2025111003480569100_JEB251075C23","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1126\/science.166.3905.613","article-title":"Seawater teleosts: evidence for a sodium-potassium exchange in the branchial sodium-excreting pump","volume":"166","author":"Maetz","year":"1969","journal-title":"Science"},{"key":"2025111003480569100_JEB251075C24","first-page":"177","article-title":"Ion Transport, osmoregulation, and acid-base balance","volume-title":"The Physiology of Fishes","author":"Marshall","year":"2006"},{"key":"2025111003480569100_JEB251075C25","doi-asserted-by":"publisher","first-page":"22749","DOI":"10.1016\/S0021-9258(18)54631-7","article-title":"Identification and localization of a dogfish homolog of human cystic fibrosis transmembrane conductance regulator","volume":"266","author":"Marshall","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2025111003480569100_JEB251075C27","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41586-018-0393-7","article-title":"A revised airway epithelial hierarchy includes CFTR-expressing ionocytes","volume":"560","author":"Montoro","year":"2018","journal-title":"Nature"},{"key":"2025111003480569100_JEB251075C28","doi-asserted-by":"publisher","first-page":"e29462","DOI":"10.1371\/journal.pone.0029462","article-title":"Morpholino gene knockdown in adult Fundulus heteroclitus: Role of SGK1 in seawater acclimation","volume":"6","author":"Notch","year":"2011","journal-title":"PLoS ONE"},{"key":"2025111003480569100_JEB251075C29","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1152\/physrev.00039.2011","article-title":"Structure and Function of TMEM16 Proteins (Anoctamins)","volume":"94","author":"Pedemonte","year":"2014","journal-title":"Physiol. Rev."},{"key":"2025111003480569100_JEB251075C30","doi-asserted-by":"publisher","first-page":"R1844","DOI":"10.1152\/ajpregu.2001.280.6.R1844","article-title":"Gill Na+-K+-2Cl\u2212 cotransporter abundance and location in Atlantic salmon: effects of seawater and smolting","volume":"280","author":"Pelis","year":"2001","journal-title":"Am. J. Physiol. Regul. Integr. Compar. Physiol."},{"key":"2025111003480569100_JEB251075C31","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41586-018-0394-6","article-title":"A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte","volume":"560","author":"Plasschaert","year":"2018","journal-title":"Nature"},{"key":"2025111003480569100_JEB251075C32","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1242\/jeb.014423","article-title":"Ionoregulatory changes during metamorphosis and salinity exposure of juvenile sea lamprey (Petromyzon marinus L.)","volume":"211","author":"Reis-Santos","year":"2008","journal-title":"J. Exp. Biol."},{"key":"2025111003480569100_JEB251075C33","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1186\/s12864-015-1677-z","article-title":"Genome-wide analysis of the ATP-binding cassette (ABC) transporter gene family in sea lamprey and Japanese lamprey","volume":"16","author":"Ren","year":"2015","journal-title":"BMC Genomics"},{"key":"2025111003480569100_JEB251075C34","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1242\/jeb.196.1.405","article-title":"The molecular basis of chloride transport in shark rectal gland","volume":"196","author":"Riordan","year":"1994","journal-title":"J. Exp. Biol."},{"key":"2025111003480569100_JEB251075C35","doi-asserted-by":"publisher","first-page":"R17","DOI":"10.1152\/ajpregu.00125.2019","article-title":"Functional characterization and osmoregulatory role of the Na+\/K+\/2Cl\u2212 cotransporter (NKCC1) in the gill of sea lamprey (Petromyzon marinus), a basal vertebrate","volume":"318","author":"Shaughnessy","year":"2020","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2025111003480569100_JEB251075C36","doi-asserted-by":"publisher","first-page":"jeb250110","DOI":"10.1242\/jeb.250110","article-title":"A Cftr-independent, Ano1-rich seawater-adaptive ionocyte in sea lamprey gills","volume":"228","author":"Shaughnessy","year":"2025","journal-title":"J. Exp. Biol."},{"key":"2025111003480569100_JEB251075C37","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/s41586-022-05331-7","article-title":"Ion regulation at gills precedes gas exchange and the origin of vertebrates","volume":"610","author":"Sackville","year":"2022","journal-title":"Nature"},{"key":"2025111003480569100_JEB251075C38","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/jez.1401990316","article-title":"Ouabain inhibition of gill Na-K-ATPase: relationship to active chloride transport","volume":"199","author":"Silva","year":"1977","journal-title":"J. Exp. Zool."},{"key":"2025111003480569100_JEB251075C39","doi-asserted-by":"publisher","first-page":"F298","DOI":"10.1152\/ajprenal.1977.233.4.F298","article-title":"Mechanism of active chloride secretion by shark rectal gland: role of Na-K-ATPase in chloride transport","volume":"233","author":"Silva","year":"1977","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"2025111003480569100_JEB251075C40","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1152\/ajpcell.1998.274.3.C715","article-title":"A divergent CFTR homologue: Highly regulated salt transport in the euryhaline teleost F. heteroclitus","volume":"274","author":"Singer","year":"1998","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2025111003480569100_JEB251075C41","doi-asserted-by":"publisher","first-page":"11376","DOI":"10.1074\/jbc.274.16.11376","article-title":"Identification by differential display of a hypertonicity-inducible inward rectifier potassium channel highly expressed in chloride cells","volume":"274","author":"Suzuki","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2025111003480569100_JEB251075C42","doi-asserted-by":"publisher","first-page":"101338","DOI":"10.1016\/j.cbd.2024.101338","article-title":"Hypersalinity tolerance of mummichogs (Fundulus heteroclitus): a branchial transcriptomic analysis","volume":"52","author":"Tao","year":"2024","journal-title":"Comp. Biochem. Physiol. D Genomics Proteomics"},{"key":"2025111003480569100_JEB251075C43","doi-asserted-by":"publisher","first-page":"e9395","DOI":"10.1002\/ece3.9395","article-title":"Salinity-induced transcriptome profiles in marine and freshwater threespine stickleback after an abrupt 6-h exposure","volume":"12","author":"Taugb\u00f8l","year":"2022","journal-title":"Ecol. Evol."},{"key":"2025111003480569100_JEB251075C44","doi-asserted-by":"publisher","first-page":"C884","DOI":"10.1152\/ajpcell.00030.2016","article-title":"Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis","volume":"311","author":"Telles","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2025111003480569100_JEB251075C45","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.cbpa.2006.06.045","article-title":"V-H+-ATPase, Na+\/K+-ATPase and NHE2 immunoreactivity in the gill epithelium of the Pacific hagfish (Epatretus stoutii)","volume":"145","author":"Tresguerres","year":"2006","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"2025111003480569100_JEB251075C46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2021.669889","article-title":"Immunologic profiling of the Atlantic salmon gill by single nuclei transcriptomics","volume":"12","author":"West","year":"2021","journal-title":"Front. Immunol."},{"key":"2025111003480569100_JEB251075C47","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1073\/pnas.91.6.2201","article-title":"Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter","volume":"91","author":"Xu","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025111003480569100_JEB251075C48","doi-asserted-by":"publisher","first-page":"R208","DOI":"10.1152\/ajpregu.00166.2023","article-title":"Molecular basis of the unique osmoregulatory strategy in the inshore hagfish, Eptatretus burgeri","volume":"327","author":"Yamaguchi","year":"2024","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2025111003480569100_JEB251075C49","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/s41586-023-06549-9","article-title":"Transgenic ferret models define pulmonary ionocyte diversity and function","volume":"621","author":"Yuan","year":"2023","journal-title":"Nature"},{"key":"2025111003480569100_JEB251075C50","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/BF00233449","article-title":"Chloride transport activation by plasma osmolarity during rapid adaptation to high salinity of Fundulus heteroclitus","volume":"143","author":"Zadunaisky","year":"1995","journal-title":"J. Membr. Biol."}],"container-title":["Journal of Experimental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jeb\/article-pdf\/doi\/10.1242\/jeb.251075\/3672814\/jeb251075.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jeb\/article-pdf\/doi\/10.1242\/jeb.251075\/3672814\/jeb251075.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:48:13Z","timestamp":1762764493000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jeb\/article\/228\/21\/jeb251075\/369781\/Salt-secreting-ionocytes-in-marine-fishes-new"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":49,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jeb.251075","relation":{},"ISSN":["0022-0949","1477-9145"],"issn-type":[{"value":"0022-0949","type":"print"},{"value":"1477-9145","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,1]]},"article-number":"jeb251075"}}