Jiang et al. reveal an elusive interaction that leads to protein translocation into the ER.
As proteins destined to enter the secretory pathway are translated, they are brought to ER channels known as translocons. The process begins when the signal sequence that tags secreted proteins first emerges from the ribosome. This peptide is bound by the signal recognition particle (SRP), which must then find its receptor (SR). Models dating back a decade propose that empty translocons are identified via interactions with the SR.
This SR–translocon interaction has not been definitely shown, however. Because both components lie in the ER membrane, experiments designed to identify the interaction have been difficult. The transient nature of the interaction—once the ribosome docks on the translocon, the SR departs—has not helped matters. But the group's new genetic evidence backs the prevailing model.
A genetic trick was provided by a yeast mutation that results in a soluble version of SR, via deletion of its transmembrane segment. Translocation efficiency was reduced in the mutants, suggesting that SR was finding the translocon at a slower rate, because it must search in three dimensions rather than just in the plane of the ER membrane.
When the Ssh1 secondary translocon, or just its β subnunit, was deleted from the soluble SR strain, the cells were severely crippled in translocation and growth. This genetic interaction suggests that soluble SR locates translocons through interactions with translocon β subunits. Deletion of the β subunit of either the primary or secondary translocon alone does not impair translocation in cells with wild-type SR, but loss of both causes a severe defect.