Post-translational translocation into the endoplasmic reticulum

Proteins destined for the endomembrane system of eukaryotic cells are typically translocated into or across the membrane of the endoplasmic reticulum and this process is normally closely coupled to protein synthesis. However, it is becoming increasingly apparent that a significant proportion of proteins are targeted to and inserted into the ER membrane post-translationally, that is after their synthesis is complete. These proteins must be efficiently captured and delivered to the target membrane, and indeed a failure to do so may even disrupt proteostasis resulting in cellular dysfunction and disease. In this review, we discuss the mechanisms by which various protein precursors can be targeted to the ER and either inserted into or translocated across the membrane post-translationally. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.

► Many proteins are post-translationally delivered to the endoplasmic reticulum.
► Multiple cytoplasmic components and molecular chaperones including TRC40/GET pathway components facilitate their delivery.
► Short secretory proteins are post-translationally translocated across the Sec61 translocon.
► The membrane integration step for tail-anchored proteins is undefined.