Membrane Protein Insertion in Mammalian Cells

Integral membrane proteins play critical roles in mammalian cells, ranging from mediating cell–cell interactions to regulating apoptosis. These increasingly diverse functions necessitated the evolution of membrane proteins with more complex biophysical properties and architectures. In turn, specialized complexes called insertases have coevolved to integrate these proteins into the appropriate lipid bilayer. Notably, key sites of membrane protein biogenesis such as the endoplasmic reticulum and the outer and inner membranes of the mitochondria rely on distinct sets of insertases that work in concert, each specializing in membrane protein segments with particular features or properties. Here, we describe recent discoveries that shed light both on the molecular mechanisms of these insertases and on the many distinct pathways required for the insertion and folding of the mammalian membrane proteome.