Oligomerization and Spatial Distribution of Kvβ1.1 and Kvβ2.1 Regulatory Subunits

Members of the regulatory Kv beta family modulate the kinetics and traffic of voltage-dependent K+ (Kv) channels. The crystal structure of Kv channels associated with Kv beta peptides suggests a alpha 4/beta 4 composition. Although Kv beta 2 and Kv beta 1 form heteromers, evidence supports that only Kv beta 2.1 forms tetramers in the absence of alpha subunits. Therefore, the stoichiometry of the Kv beta oligomers fine-tunes the activity of hetero-oligomeric Kv channel complexes. We demonstrate that Kv beta subtypes form homo- and heterotetramers with similar affinities. The Kv beta 1.1/Kv beta 2.1 heteromer showed an altered spatial distribution in lipid rafts, recapitulating the Kv beta 1.1 pattern. Because Kv beta 2 is an active partner of the Kv1.3-TCR complex at the immunological synapse (IS), an association with Kv beta 1 would alter this location, shaping the immune response. Differential regulation of Kv beta s influences the traffic and architecture of the Kv beta heterotetramer, modulating Kv beta-dependent physiological responses.

Automated summary

Members of the regulatory Kv beta family play a role in modulating the kinetics and traffic of voltage-dependent Kv channels. The formation of heteromeric complexes between Kv beta subtypes influences the spatial distribution in lipid rafts and can alter the immune response. Differentially regulating Kv beta subtypes can modulate Kv beta-dependent physiological responses and the architecture of Kv beta heterotetramers.