Many proteins are translocated across or integrated into a cellular membrane without disrupting its integrity, although it is difficult to imagine how such macromolecular transmembrane movement can occur without simultaneously allowing significant small-molecule and ion diffusion across the bilayer. Recent studies have identified some molecular mechanisms that are involved in maintaining the permeability barrier of the endoplasmic reticulum membrane during co-translational protein translocation and integration. These mechanisms are both simple and direct in concept, but are operationally complex and require the co-ordinated and regulated interaction of several multicomponent complexes.

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