Voltage sensor mutations differentially target misfolded K+ channel subunits to proteasomal and non-proteasomal disposal pathways.

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Myers MP,Khanna R,Lee EJ,Papazian DM

doi

10.1016/j.febslet.2004.05.023

keywords:

subject

Has Abstract

pub_date

2004-06-18 00:00:00

pages

110-6

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579304006246

journal_volume

568

pub_type

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