THE PROTEIN-CONTENT AND MORPHOGENESIS OF ZYMOGEN GRANULES

When zymogen granules, the secretion granules of pancreatic acinar cel ls, fill, secretory product is accumulated in immature granules, conde nsing vacuoles. Mature granules are formed when this product !protein) condenses into an osmotically inactive aggregate and, bulk water is e xpelled. This hypothesis for granule morphogenesis has two elements. T he first is that immature granules are precursors to mature granules. The second is that a particular maturational event, condensation, whic h involves the aggregation of protein, takes place. These hypotheses l ead to two straightforward predictions. One, that condensing vacuoles on average, should contain less protein than filled or mature granules . And two, that, due to condensation, mature granules should contain p rotein at a common concentration. In the current work, both of these p redictions were tested using measurements of the protein content of in dividual granules acquired by X-ray microscopy. Neither prediction was affirmed by the experimental results. First, there was no distinguish able difference in the distribution of protein between immature and ma ture granules. Second, the protein concentration of mature granules va ried widely between preparations, although granules from the same prep aration had similar concentrations. From the data we conclude that: I) mature granules and condensing vacuoles are different, though not nec essarily unrelated, types of secretory vesicle, and not two forms of t he same object; 2) as such, condensing vacuoles are not precursors to mature granules; 3) all granules do not contain protein at one particu lar concentration when ''full,'' or mature; 4) granule maturation does not involve a condensation step; 5) concentration is not determined b y such physical limits as the space available for protein packing or c ondensation; and 6) the amount of protein contained is physiologically regulated.