The courtship and marriage of K+ channel subunits

Assembly of oligomeric membrane proteins is complex. It is even more complicated in the case of a polytopic protein such as a voltage-gated K+ channel. However, one can engineer a particular biophysical function of such a channel to reveal the prior history of its subunits during assembly. These functional tagging experiments entail either heterologous expression of a wild-type subunit with a mutant subunit, or heterologous expression of a mutant subunit in a cell expressing endogenous wildtype channels. The method of analysis of the appropriately modified function assumes a binomial distribution for the random formation of homo- and heteromultimeric channels. Application of this general strategy to the T lymphocyte K+ channel, Kv1.3, has revealed that subunits are recruited randomly into tetramers from mixed pools of wild-type and mutant monomers, that tetramers in the plasma membrane of the T cell do not dissociate, and that temporal, but not spatial, segregation of wild-type and mutant subunits occurs within this cell.