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Cells known to spew secretory protein granules had been helpful in deciphering and defining the secretory pathway. But what happened when secretion systems were turned off? Lysosomes were known to degrade foreign proteins taken up by cells and even autodigest intracellular membranous structures—but what was the fate of excess endogenous protein?

To ask that question, Smith and Farquhar (1966) needed a secretion system that could be manipulated in the lab (and without the benefit of today's inducible gene expression systems). Lactating rats provided prolactin-secreting pituitary cells that fit the bill as “it was easy to cut off secretion by removing the suckling babies and then ask, how would the cells adapt?” says Marilyn Farquhar (University of California, San Diego, CA).

The cells, says Farquhar, were “devoted to pushing out prolactin,” at least until the babies were removed. At that point the duo brought in the...

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