RGD Reference Report - KCNE1 and KCNE2 inhibit forward trafficking of homomeric N-type voltage-gated potassium channels. - Rat Genome Database

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KCNE1 and KCNE2 inhibit forward trafficking of homomeric N-type voltage-gated potassium channels.

Authors: Kanda, VA  Lewis, A  Xu, X  Abbott, GW 
Citation: Kanda VA, etal., Biophys J. 2011 Sep 21;101(6):1354-63. doi: 10.1016/j.bpj.2011.08.015. Epub 2011 Sep 20.
RGD ID: 7242916
Pubmed: (View Article at PubMed) PMID:21943416
DOI: Full-text: DOI:10.1016/j.bpj.2011.08.015

Potassium currents generated by voltage-gated potassium (Kv) channels comprising alpha-subunits from the Kv1, 2, and 3 subfamilies facilitate high-frequency firing of mammalian neurons. Within these subfamilies, only three alpha-subunits (Kv1.4, Kv3.3, and Kv3.4) generate currents that decay rapidly in the open state because an N-terminal ball domain blocks the channel pore after activation-a process termed N-type inactivation. Despite its importance to shaping cellular excitability, little is known of the processes regulating surface expression of N-type alpha-subunits, versus their slowly inactivating (delayed rectifier) counterparts. Here we found that currents generated by homomeric Kv1.4, Kv3.3, and Kv3.4 channels are all strongly suppressed by the single transmembrane domain ancillary (beta) subunits KCNE1 and KCNE2. A combination of electrophysiological, biochemical, and immunofluorescence analyses revealed this suppression is due to KCNE1 and KCNE2 retaining Kv1.4 and Kv3.4 intracellularly, early in the secretory pathway. The retention is specific, requires alpha-beta coassembly, and does not involve the dynamin-dependent endocytosis pathway. However, the small fraction of Kv3.4 that escapes KCNE-dependent retention is regulated by dynamin-dependent endocytosis. The findings illustrate two contrasting mechanisms controlling surface expression of N-type Kv alpha-subunits and therefore, potentially, cellular excitability and refractory periods.

Annotation

Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Kcna1  (potassium voltage-gated channel subfamily A member 1)
Kcna4  (potassium voltage-gated channel subfamily A member 4)
Kcnc4  (potassium voltage-gated channel subfamily C member 4)
Kcne1  (potassium voltage-gated channel subfamily E regulatory subunit 1)
Kcne2  (potassium voltage-gated channel subfamily E regulatory subunit 2)


Additional Information