TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Wesch, Diana
A1  - Althaus, Mike
A1  - Miranda, Pablo
A1  - Cruz-Muros, Ignacio
A1  - Fronius, Martin
A1  - Gonzalez-Hernandez, Tomas
A1  - Clauss, Wolfgang G.
A1  - Alvarez de la Rosa, Diego
A1  - Giraldez, Teresa
T1  - Differential N termini in epithelial Na+ channel δ-subunit isoforms modulate channel trafficking to the membrane
JF  - American Journal of Physiology: Cell physiology
N2  - Wesch D, Althaus M, Miranda P, Cruz-Muros I, Fronius M, Gonzalez-Hernandez T, Clauss WG, de la Rosa DA, Giraldez T. Differential N termini in epithelial Na+ channel delta-subunit isoforms modulate channel trafficking to the membrane. Am J Physiol Cell Physiol 302: C868-C879, 2012. First published December 7, 2011; doi: 10.1152/ajpcell.00255.2011.-The epithelial Na+ channel (ENaC) is a heteromultimeric ion channel that plays a key role in Na+ reabsorption across tight epithelia. The canonical ENaC is formed by three analogous subunits, alpha, beta, and gamma. A fourth ENaC subunit, named delta, is expressed in the nervous system of primates, where its role is unknown. The human delta-ENaC gene generates at least two splice isoforms, delta(1) and delta(2), differing in the N-terminal sequence. Neurons in diverse areas of the human and monkey brain differentially express either delta(1) or delta(2), with few cells coexpressing both isoforms, which suggests that they may play specific physiological roles. Here we show that heterologous expression of delta(1) in Xenopus oocytes and HEK293 cells produces higher current levels than delta(2). Patch-clamp experiments showed no differences in single channel current magnitude and open probability between isoforms. Steady-state plasma membrane abundance accounts for the dissimilarity in macroscopic current levels. Differential trafficking between isoforms is independent of beta- and gamma-subunits, PY-motif-mediated endocytosis, or the presence of additional lysine residues in delta(2)-N terminus. Analysis of delta(2)-N terminus identified two sequences that independently reduce channel abundance in the plasma membrane. The delta(1) higher abundance is consistent with an increased insertion rate into the membrane, since endocytosis rates of both isoforms are indistinguishable. Finally, we conclude that delta-ENaC undergoes dynamin-independent endocytosis as opposed to alpha beta gamma-channels.
KW  - endocytosis
KW  - insertion
KW  - dynamin
SN  - 0363-6143
SS  - 0363-6143
U6  - https://doi.org/10.1152/ajpcell.00255.2011
DO  - https://doi.org/10.1152/ajpcell.00255.2011
PM  - 22159085
VL  - 302
IS  - 6
PB  - American Physiological Society
ER  -