However, shortly after the synthesis actually begins, it stops, because the ribosomes are transported into the cytoplasmic side of the endoplasmic reticulum's membrane and the polypeptide synthesis then resumes and the growing polypeptide chain extends into the er lumen. Now, the question is, what exactly is the mechanism by which the ribosome knows to migrate onto the endoplasmic reticulum? So this should be not ribosome, but endoplasmic reticulum. So let's designate this as Er. So what distinguishes the polypeptides destined to remain inside the side of plasma, the cell, compared to those that are ultimately secreted or end up being inside the plasma membrane of that cell? So, basically, it's the sequence of amino acids known as the signal sequence.