ArticleThe EMBO journal1994
An SH3 binding region in the epithelial Na+ channel (alpha rENaC) mediates its localization at the apical membrane.
Article in The EMBO journal, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 223 citations in OpenAlex.
- Contribution of murine strain background to NabioRxiv : the preprint server for biology · 2026Article
- Epithelial NaComprehensive Physiology · 2024Review
- Ion channel TRPV2 is critical in enhancing B cell activation and function.The Journal of experimental medicine · 2024Article
- The diverse functions of the DEG/ENaC family: linking genetic and physiological insights.The Journal of physiology · 2023Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial NaScientific reports · 2021Article
- Cav3.2 calcium channel interactions with the epithelial sodium channel ENaC.Molecular brain · 2019Article
- T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B.Molecular brain · 2018Article
- The potential role of spectrin network in the mechanotransduction of MLO-Y4 osteocytes.Scientific reports · 2017Article
- Review
- The Epithelial Sodium Channel and the Processes of Wound Healing.BioMed research international · 2016Review
- Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells.American journal of physiology. Renal physiology · 2014Article
- The role of ENaC in vascular endothelium.Pflugers Archiv : European journal of physiology · 2014Review
- Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells.Nature reviews. Nephrology · 2014Review
- Acute effects of cigarette smoke extract on alveolar epithelial sodium channel activity and lung fluid clearance.American journal of respiratory cell and molecular biology · 2013Article
- Epithelial Na(+) channel regulation by cytoplasmic and extracellular factors.Experimental cell research · 2012Review
- The plasma membrane potential and the organization of the actin cytoskeleton of epithelial cells.International journal of cell biology · 2012Article
- Involvement of the calcium-sensing receptor in human taste perception.The Journal of biological chemistry · 2010Article
- Membrane domains based on ankyrin and spectrin associated with cell-cell interactions.Cold Spring Harbor perspectives in biology · 2009Review
- Cell migration in BeWo cells and the role of epithelial sodium channels.The Journal of membrane biology · 2009Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amiloride-sensitive Na+ channel constitutes the rate-limiting step for Na+ transport in epithelia. Immunolocalization and electrophysiological studies have demonstrated that this channel is localized at the apical membrane of polarized epithelial cells. This localization is essential for proper channel function in Na+ transporting epithelia. In addition, the channel has been shown to associate with the cytoskeletal proteins ankyrin and alpha-spectrin in renal epithelia. However, the molecular mechanisms underlying the cytoskeletal interactions and apical membrane localization of this channel are largely unknown. In this study we show that the putative pore forming subunit of the rat epithelial (amiloride-sensitive) Na+ channel (alpha ENaC) binds to alpha-spectrin in vivo, as determined by co-immunoprecipitation. This binding is mediated by the SH3 domain of alpha-spectrin which binds to a unique proline-rich sequence within the C-terminal region of alpha rENaC. Accordingly, the C-terminal region is sufficient to mediate binding to intact alpha-spectrin from alveolar epithelial cell lysate. When microinjected into the cytoplasm of polarized primary rat alveolar epithelial cells, a recombinant fusion protein containing the C-terminal proline-rich region of alpha rENaC localized exclusively to the apical area of the plasma membrane, as determined by confocal microscopy. This localization paralleled that of alpha-spectrin. In contrast, microinjected fusion protein containing the N-terminal (control) protein of alpha rENaC remained diffuse within the cytoplasm. These results suggest that an SH3 binding region in alpha rENaC mediates the apical localization of the Na+ channel. Thus, cytoskeletal interactions via SH3 domains may provide a novel mechanism for retaining proteins in specific membranes of polarized epithelial cells.
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