Making membrane proteins at the mammalian endoplasmic reticulum

Whereas protein biogenesis at the endoplasmic reticulum is well understood in the case of secretory proteins and simple membrane proteins, much less is known about the synthesis of multi-spanning integral membrane proteins. While it is clear that the multiple membrane-spanning domains of these proteins must be inserted into the lipid bilayer during biosynthesis, the mechanism by which their integration is achieved and their subsequent folding/assembly are poorly defined. In this review, we summarize our current understanding of protein synthesis at the endoplasmic reticulum and highlight specific features that are relevant to the biogenesis of multi-spanning membrane proteins.