Translocation of proteins across the endoplasmic reticulum membrane

Secretory protein biogenesis begins with the insertion of a preprotein into the lumen of the endoplasmic reticulum (ER). This insertion event, known as ER protein translocation, can occur either posttranslationally, in which the preprotein is completely synthesized on cytosolic ribosomes before being translocated, or cotranslationally, in which membrane-associated ribosomes direct the nascent polypeptide chain into the ER concomitant with polypeptide elongation. In either case, preproteins are targeted to the ER membrane through specific interactions with cytosolic and/or ER membrane factors. The preprotein is then transferred to a multiprotein translocation machine in the ER membrane that includes a pore through which the preprotein passes into the ER lumen. The energy required to drive protein translocation may derive either from the coupling of translation to translocation (during cotranslational translocation) or from ER lumenal molecular chaperones that may harness the preprotein or regulate the translocation machinery (during posttranslational translocation).