Characterization of an early-diverging KCNE potassium-channel auxiliary subunit in the jawless vertebrate lamprey

In a recent study, researchers have examined the KCNE proteins, which are auxiliary subunits of voltage-gated K+ channels known as KCNQ1. These KCNE proteins, specifically KCNQ1-KCNQ1 complexes, have been extensively investigated in various jawed vertebrates such as zebrafish and humans. However, prior research has not extensively explored KCNE subunits found in earlier-diverging vertebrates, particularly in lamprey, a jawless vertebrate.

The study focused on characterizing a single KCNE-like gene in lamprey, which was designated as kcne0. The researchers found that kcne0 exhibits moderate amino acid sequence similarity to its counterparts KCNE1–6 but lacks a strong similarity to any single isoform. Both kcnq1 and kcne0 transcripts were detected in multiple lamprey organs, indicating their presence in various parts of the organism.

When kcne0 was co-expressed with lamprey KCNQ1, it produced a constitutively active current, which was similar to the effect observed with KCNE3. However, the impact of kcne0 on KCNQ1 varied less effectively when compared to KCNQ1 from other species. This suggests a species-specific tuning of KCNQ1-KCNQ1 compatibility. Furthermore, the researchers introduced an intracellular tetra-leucine motif into kcne0, similar to the one found in KCNE4.

This modification resulted in a significant reduction of KCNQ1 current amplitude, conferring a KCNE4-like inhibitory effect.

In conclusion, this study offers a functional reference for comparing the modulation of KCNQ1 by KCNE proteins across different vertebrates. The findings also shed light on an underlying compatibility mechanism that may be responsible for the observed differences in KCNQ1-KCNQ1 interactions.