Suraj Saksena, Arthur Johnson, and colleagues (Texas A&M University, College Station, TX) now show that INM-bound proteins are sorted as they enter the ER through the translocon. They find that transmembrane sequences of both viral and mammalian INM proteins cross-link to Sec61α and TRAM, which are fundamental translocon proteins. Association with TRAM continues even though the growing peptide is long enough to release the transmembrane segment into the bilayer.
Only two native non-INM proteins have been found to be adjacent to TRAM. “This sent us a signal that TRAM might act as a recognition component,” says Johnson. “This goes along with my belief that the cell doesn't let anything happen randomly.”
After leaving the translocon, the viral INM proteins were handed off to other viral proteins that are known to be needed for INM targeting. Now, the authors are seeking the endogenous nontranslocon components that take care of this job. ▪