Getting to the inner circle

Contiguity 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 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...