Oligomerization and Spatial Distribution of Kv beta 1.1 and Kv beta 2.1 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.