It's a chaperone … it's a gatekeeper … it's BiP

Imagine inserting a piece of string into an inflated balloon without letting any of the air out. Ananalogous problem confronts cells in the production of integral membrane-spanning proteins, which must be inserted partway into the ER without letting the ER calcium stores leak into the cytoplasm. On page 261, Haigh and Johnson show that the ER lumenal chaperone protein BiP controls one end of a double door system at the translocon, the pore through which nascent proteins enter the ER, and propose a model to explain how the cell accomplishes the daunting task of regulating this double door.

On the cytoplasmic side of the ER membrane, the ribosome binds to the translocon to seal it while translocating a nascent polypeptide into the ER lumen. But the ribosome must break this seal to allow a cytoplasmic domain to extend into the...