Sorting proteins to the rough endoplasmic reticulum

The ER acts as an intracellular store of Ca²⁺ ions, which are used in cell signalling. The ER membrane is the site of production for nearly all of the transmembrane proteins, and lipids, for all of the cell’s organelles.

• Protein synthesis starts in cytosol
• Proteins contain a N-terminal signal sequence
• Signal sequence binds receptor on RER; ribosome associates with RER
• Polypeptide synthesis completed on RER
• Protein translocates into RER membrane or lumen during synthesis
• Signal peptide cleaved

There are two mechanisms of the transport of proteins into the ER.

Ribosomes bind to the ER membrane during co-translational translocation. By contrast, cytosolic ribosomes complete the synthesis of a protein and release it prior to post-translational translocation. In both cases, the protein is directed to the ER by an ER signal sequence.

The ER captures selected proteins from the cytosol as they are being synthesised. There are two types of these proteins:

Transmembrane proteins and water-soluble proteins:

• Water-soluble proteins are fully translocated across the ER membrane and are released into the ER lumen. These proteins are destined for secretion or for residence in the lumen of the ER or of another organelle.
• Transmembrane proteins are only partly translocated across the ER membrane, and therefore become embedded in it. Some of the transmembrane proteins function in the ER, but many are sent to the plasma membrane or the membranes of other organelles.