Voltage sensor mutations differentially target misfolded K+ channel subunits to proteasomal and non‐proteasomal disposal pathways
Open Access
- 25 May 2004
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 568 (1-3) , 110-116
- https://doi.org/10.1016/j.febslet.2004.05.023
Abstract
In Shaker K+ channels, formation of an electrostatic interaction between two charged residues, D316 and K374 in transmembrane segments S3 and S4, respectively, is a key step in voltage sensor biogenesis. Mutations D316K and K374E disrupt formation of the voltage sensor and lead to endoplasmic reticulum retention. We have now investigated the fates of these misfolded proteins. Both are significantly less stable than the wild‐type protein. D316K is degraded by cytoplasmic proteasomes, whereas K374E is degraded by a lactacystin‐insensitive, non‐proteasomal pathway. Our results suggest that the D316K and K374E proteins are misfolded in recognizably different ways, an observation with implications for voltage sensor biogenesis.Keywords
This publication has 49 references indexed in Scilit:
- Transient calnexin interaction confers long-term stability on folded K+ channel protein in the ERJournal of Cell Science, 2004
- X-ray structure of a voltage-dependent K+ channelNature, 2003
- Glycoprotein Quality Control in the Endoplasmic ReticulumJournal of Biological Chemistry, 2001
- Degradation of Human Thyroperoxidase in the Endoplasmic Reticulum Involves Two Different Pathways Depending on the Folding State of the ProteinJournal of Biological Chemistry, 2000
- Mannose Trimming Targets Mutant α2-Plasmin Inhibitor for Degradation by the ProteasomeJournal of Biological Chemistry, 2000
- Inhibition of Glucose Trimming with Castanospermine Reduces Calnexin Association and Promotes Proteasome Degradation of the α-Subunit of the Nicotinic Acetylcholine ReceptorJournal of Biological Chemistry, 1998
- The Structure of the Potassium Channel: Molecular Basis of K + Conduction and SelectivityScience, 1998
- Intersubunit Interaction between Amino- and Carboxyl-Terminal Cysteine Residues in Tetrameric Shaker K+ ChannelsBiochemistry, 1996
- Conserved cysteine residues in the Shaker K+ channel are not linked by a disulfide bondBiochemistry, 1995
- Determination of the subunit stoichiometry of a voltage-activated potassium channelNature, 1991