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Differential plasma membrane abundance of epithelial sodium channel δ subunit splice isoforms
Author(s) -
Rosa Diego Alvarez,
Wesch Diana,
Althaus Mike,
Miranda Pablo,
Fronius Martin,
Clauss Wolfgang G,
Giraldez Teresa
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1041.45
Subject(s) - epithelial sodium channel , xenopus , gene isoform , protein subunit , endocytosis , microbiology and biotechnology , biology , reabsorption , chemistry , endocrinology , kidney , biochemistry , sodium , gene , receptor , organic chemistry
Epithelial Na + channel (ENaC) α, β and γ subunits form heterotrimeric Na + ‐selective ion channels with a well‐characterized role in Na + reabsorption across tight epithelia, such as the distal tubule of the kidney. However, channels formed by other subunit combinations may be physiologically relevant. In humans and primates there is a fourth ENaC subunit, named δ, which is expressed in various organs such as pancreas, nervous system and lung. The human δ ENaC gene produces at least two splice isoforms (δ1 and δ2) that differ in their n‐terminal intracellular sequence. When expressed in Xenopus oocytes, δ1 Na + transport activity is approximately four‐fold higher than δ2, regardless of the presence of accessory β and γ subunits. Single channel analysis and plasma membrane abundance of δ1 and δ2 show that the main difference between isoforms is their steady‐state plasma membrane abundance. This difference is independent of PY‐motif mediated endocytosis or the presence of additional lysine residues in the n‐terminus of δ2. We have delineated a sequence motif in δ2 responsible for the lower plasma membrane expression. Experiments are underway to determine whether this sequence differentially controls channel insertion, endocytosis or both. This work was funded by the Spanish Ministry of Science (grants FIS‐PS09/00406, Consolider CSD‐2008‐00005 and HD2008‐0025) and the German Academic Exchange Service (DAAD).