RGD Reference Report - KCNE1 and KCNE2 provide a checkpoint governing voltage-gated potassium channel a-subunit composition. - Rat Genome Database

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KCNE1 and KCNE2 provide a checkpoint governing voltage-gated potassium channel a-subunit composition.

Authors: Kanda, Vikram A  Lewis, Anthony  Xu, Xianghua  Abbott, Geoffrey W 
Citation: Kanda VA, etal., Biophys J. 2011 Sep 21;101(6):1364-75. doi: 10.1016/j.bpj.2011.08.014. Epub 2011 Sep 20.
RGD ID: 12910700
Pubmed: (View Article at PubMed) PMID:21943417
DOI: Full-text: DOI:10.1016/j.bpj.2011.08.014

Voltage-gated potassium (Kv) currents generated by N-type α-subunit homotetramers inactivate rapidly because an N-terminal ball domain blocks the channel pore after activation. Hence, the inactivation rate of heterotetrameric channels comprising both N-type and non-N-type (delayed rectifier) α-subunits depends upon the number of N-type α-subunits in the complex. As Kv channel inactivation and inactivation recovery rates regulate cellular excitability, the composition and expression of these heterotetrameric complexes are expected to be tightly regulated. In a companion article, we showed that the single transmembrane segment ancillary (ß) subunits KCNE1 and KCNE2 suppress currents generated by homomeric Kv1.4, Kv3.3, and Kv3.4 channels, by trapping them early in the secretory pathway. Here, we show that this trapping is prevented by coassembly of the N-type α-subunits with intra-subfamily delayed rectifier α-subunits. Extra-subfamily delayed rectifier α-subunits, regardless of their capacity to interact with KCNE1 and KCNE2, cannot rescue Kv1.4 or Kv3.4 surface expression unless engineered to interact with them using N-terminal A and B domain swapping. The KCNE1/2-enforced checkpoint ensures N-type α-subunits only reach the cell surface as part of intra-subfamily mixed-α complexes, thereby governing channel composition, inactivation rate, and-by extension-cellular excitability.

Annotation

Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Kcna4  (potassium voltage-gated channel subfamily A member 4)
Kcnb1  (potassium voltage-gated channel subfamily B member 1)
Kcnc1  (potassium voltage-gated channel subfamily C member 1)
Kcnc2  (potassium voltage-gated channel subfamily C member 2)
Kcnc4  (potassium voltage-gated channel subfamily C member 4)
Kcne1  (potassium voltage-gated channel subfamily E regulatory subunit 1)


Additional Information