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Domain analysis of Kv6.3, an electrically silent channel
Author(s) -
Ottschytsch Natacha,
Raes Adam L.,
Timmermans JeanPierre,
Snyders Dirk J.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.090142
Subject(s) - er retention , endoplasmic reticulum , protein subunit , transmembrane domain , context (archaeology) , transmembrane protein , potassium channel , biophysics , microbiology and biotechnology , intracellular , chemistry , voltage gated ion channel , membrane potential , subcellular localization , c terminus , biology , biochemistry , ion channel , membrane , cytoplasm , receptor , amino acid , paleontology , mutant , gene
The subunit Kv6.3 encodes a voltage‐gated potassium channel belonging to the group of electrically silent Kv subunits, i.e. subunits that do not form functional homotetrameric channels. The lack of current, caused by retention in the endoplasmic reticulum (ER), was overcome by coexpression with Kv2.1. To investigate whether a specific section of Kv6.3 was responsible for ER retention, we constructed chimeric subunits between Kv6.3 and Kv2.1, and analysed their subcellular localization and functionality. The results demonstrate that the ER retention of Kv6.3 is not caused by the N‐terminal A and B box (NAB) domain nor the intracellular N‐ or C‐termini, but rather by the S1–S6 core protein. Introduction of individual transmembrane segments of Kv6.3 in Kv2.1 was tolerated, with the exception of S6. Indeed, introduction of the S6 domain of Kv6.3 in Kv2.1 was enough to cause ER retention, which was due to the C‐terminal section of S6. The S4 segment of Kv6.3 could act as a voltage sensor in the Kv2.1 context, albeit with a major hyperpolarizing shift in the voltage dependence of activation and inactivation, apparently caused by the presence of a tyrosine in Kv6.3 instead of a conserved arginine. This study suggests that the silent behaviour of Kv6.3 is largely caused by the C‐terminal part of its sixth transmembrane domain that causes ER retention of the subunit.