It was cell biology's version of the ship in the bottle. How do proteins a cell intends to secrete end up in the endoplasmic reticulum? Winkling out the details of the translocation mechanism that spirits these proteins into the ER required more than 20 years and earned Günter Blobel of Rockefeller University the 1999 Nobel Prize in Physiology or Medicine.
Another Rockefeller laureate, George Palade, had demonstrated that ribosomes free in the cytoplasm manufactured nonsecreted proteins, whereas ribosomes stuck to the ER made proteins for export. Cell biologists searched in vain for distinctions between free and attached ribosomes that might explain their contrasting behavior. A new assistant professor at Rockefeller and Palade's protege, Blobel suspected that the difference must lie in the proteins themselves. He and colleague David Sabatini conjectured that secretory proteins might carry a short segment near the NH2 terminus (Blobel and...
