Abstract
FXYD3 increases Na + transport across human airway epithelia
The FASEB journal, Vol.36 Suppl 1(S1), p.n/a
05/2022
DOI: 10.1096/fasebj.2022.36.S1.R6263
PMID: 35556371
Abstract
The Na/K ATPase localizes within the basolateral membrane of most epithelia, where Na/K ATPase activity mediates Na
absorption. The Na/K ATPase requires its alpha subunit for ion transport and its beta subunit for proper trafficking to the plasma membrane. The non-essential gamma subunit of the Na/K ATPase modifies Na/K ATPase activity. Datasets within the NIH Gene Expression Omnibus indicate that FXYD3, a Na/K ATPase gamma subunit, is highly expressed by human airway epithelia. However, how FXYD3 affects airway epithelial function remains unstudied. In addition to binding the Na/K ATPase, FXYD3 can bind and modify H/K ATPases in heterologous expression systems. The H/K ATPase ATP12A acidifies human airway surface liquid. Therefore, we evaluated the role of FXYD3 in both acid secretion and Na
absorption across human airway epithelia. Single cell RNA sequencing revealed high FXYD3 expression for all the airway cell types, and immunocytochemistry revealed FXYD3 expression within the basolateral membrane of airway epithelia. Consistent with basolateral FXYD3 localization, the airway surface liquid pH, established in part by apical H/K ATPase, was unaffected by siRNA-mediated knockdown of FXYD3. FXYD3 knockdown decreased amiloride-sensitive short-circuit currents (~20% in NaCl and ~40% in NaGluconate solutions), a finding that is consistent with FXYD3 increasing Na/K ATPase activity. Consequently, fluid absorption across airway epithelia was reduced by ~20% with FXYD3 knockdown. FXYD3 may be required to efficiently return the airway surface liquid to homeostatic volumes after fluid secretion into the proximal airways.
Details
- Title: Subtitle
- FXYD3 increases Na + transport across human airway epithelia
- Creators
- Camilo Cano Portillo - Internal Medicine, University of Iowa, Iowa City, IARaul Villacreses - University of IowaAndrew Thurman - University of IowaAlejandro Pezzulo - University of IowaJoseph Zabner - University of IowaIan M Thornell - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.36 Suppl 1(S1), p.n/a
- DOI
- 10.1096/fasebj.2022.36.S1.R6263
- PMID
- 35556371
- NLM abbreviation
- FASEB J
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Grant note
- P01HL051670 / NHLBI NIH HHS K01HL140261 / NHLBI NIH HHS Cystic Fibrosis Foundation University
- Language
- English
- Date published
- 05/2022
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984363558502771
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