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Regulation of Kvl channel trafficking by the mamba snake neurotoxin dendrotoxin K
Author(s) -
Vacher Helene,
Mohapatra Durga P.,
Misonou Hiroaki,
Trimmer James S.
Publication year - 2007
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/fj.06-7229com
Subject(s) - potassium channel , endoplasmic reticulum , microbiology and biotechnology , chemistry , shaker , biophysics , er retention , protein subunit , ion channel , biochemistry , biology , receptor , gene , physics , quantum mechanics , mutant , vibration
Modulation of voltage‐gated potassium (Kv) channel surface expression can profoundly affect neuronal excitability. Some, but not all, mammalian Shaker or Kvl α subunits contain a dominant endoplasmic reticulum (ER) retention signal in their pore region, preventing surface expression of Kvl.l homotet‐rameric channels and of heteromeric Kvl channels containing more than one Kvl.l subunit. The critical amino acid residues within this ER pore‐region retention signal are also critical for high‐affinity binding of snake dendrotoxins (DTX). This suggests that ER retention may be mediated by an ER protein with a domain structurally similar to that of DTX. One facet of such a model is that expression of soluble DTX in the ER lumen should compete for binding to the retention protein and allow for surface expression of retained Kvl.l. Here, we show that luminal DTX expression dramatically increased both the level of cell surface Kvl.l immunofluorescence staining and the proportion of Kvl.l with processed./V‐linked oligosaccharides. Electrophysiological analyses showed that luminal DTX expression led to significant increases in Kvl. 1 currents. Together, these data showed that luminal DTX expression increases surface expression of functional Kvl.l homotetrameric channels and support a model whereby a DTX‐like ER protein regulates abundance of cell surface Kvl channels.—Vacher, H., Mohapatra, D. P., Misonou, H., Trimmer, J. S. Regulation of Kv1 channel trafficking by the mamba snake neurotoxin dendrotoxin K. FASEB J. 21, 906–914(2007)