Getting to the inner circle

Getting to the inner circle ontiguity between the ER and the nuclear envelope means nuclear membrane proteins have a direct shot to their target. In fact, inner nuclear membrane (INM) proteins were thought to need only to diffuse to the nucleus, pass through the nuclear pore, and then be retained by nuclear-localized binding partners. But new results suggest a more active process. 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 Sec61 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.