Plasma membrane receives new proteins from the secretion pathway that is the mitochondria and proteins being synthesized on the ribosomal machinery of cells. They are either first inserted co-translationally into the membrane of the endoplasmic reticulum, or post-translationally into membranes of mitochondria, the nucleus, or peroxisomes.
Proteins from the secretion pathway are anchored in the plasma membrane by covalently attached lipids or glycolipids. Members of one class of these proteins are inserted into the outer leaflet of the plasma membrane by glycosylphosphatidylinositol (GPI) anchors. GPI anchors are added to certain proteins that have been transferred into the endoplasmic reticulum and are anchored in the membrane by a C-terminal transmembrane region The transmembrane region is cleaved as the GPI anchor is added, so these proteins remain attached to the membrane only by the glycolipid. Since the polypeptide chains of GPI-anchored proteins are transferred into the endoplasmic reticulum, they are glycosylated and exposed on the surface of the cell following transport to the plasma membrane.
Other proteins are anchored in the inner leaflet of the plasma membrane by covalently attached lipids. Rather than being processed through the secretory pathway, these proteins are synthesized on free cytosolic ribosomes and then modified by the addition of lipids. These modifications include the addition of myristic acid (a 14-carbon fatty acid) to the amino terminus of the polypeptide chain, the addition of palmitic acid (16 carbons) to the side chains of cysteine residues, and the addition of prenyl groups (15 or 20 carbons) to the side chains of carboxy-terminal cysteine residues. In some cases, these proteins (many of which behave as peripheral membrane proteins) are targeted to the plasma membrane by positively charged regions of the polypeptide chain as well as by the attached lipids.
The new proteins in the moves across and within the membrane through membrane diffusion.