The protein content and morphogenesis of zymogen granules

Abstract

When zymogen granules, the secretion granules of pancreatic acinar cells, fill, secretory product is accumulated in immature granules, condensing vacuoles. Mature granules are formed when this product (protein) condenses into an osmotically inactive aggregate and, bulk water is expelled. This hypothesis for granule morphogenesis has two elements. The first is that immature granules are precursors to mature granules. The second is that a particular maturational event, condensation, which involves the aggregation of protein, takes place. These hypotheses lead 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 protein at a common concentration. In the current work, both of these predictions were tested using measurements of the protein content of individual granules acquired by X-ray microscopy. Neither prediction was affirmed by the experimental results. First, there was no distinguishable difference in the distribution of protein between immature and mature granules. Second, the protein concentration of mature granules varied widely between preparations, although granules from the same preparation had similar concentrations. From the data we conclude that: 1) mature granules and condensing vacuoles are different, though not necessarily unrelated, types of secretory vesicle, and not two forms of the same object; 2) as such, condensing vacuoles are not precursors to mature granules; 3) all granules do not contain protein at one particular concentration when "full," or mature; 4) granule maturation does not involve a condensation step; 5) concentration is not determined by such physical limits as the space available for protein packing or condensation; and 6) the amount of protein contained is physiologically regulated.

Selective exocytosis of zymogen granules induces non-parallel secretion in short-term cholecystokinin-stimulated rats

“…However, the enzyme/FSC ratio indicated that the two enzymes were more concentrated in each zymogen granule, because the granules were smaller in CCKstimulated rats. In agreement with the findings of Goncz et al (1995), our results suggest that the concentrations of the intragranular enzyme do not depend on physical limitations, but can be physiologically regulated. The intragranular amylase/trypsinogen ratio revealed that the granules released at the begining of CCK infusion carry a proportional admixture of both enzymes.…”

Regulation of secretory granule size by the precise generation and fusion of unit granules

“…ratio of immature granule volume to mature unit granule volume) of between 7.7:1 and 9.2:1 [17]. The notion that a process of condensation can result in a reduction of granule volume without substantial change in the protein content of the granule is supported by the work of Goncz et al [78] who estimated the protein content of individual CVs and mature zymogen granules in rat pancreatic acinar cells by X-ray microscopy. Pulse labelling of mouse pancreatic acinar cells with 3 H-glycine also supports the conclusion that immature granules undergo a progressive reduction in size during their maturation [25].…”

Exocytosis from rat submandibular granular tubules during cyclocytidine stimulation shows unusual features, including changes in the granule membrane

“…Exocytosis is known to be a complex procedure leading to the extrusion of preformed secretory material (Arvan and Castle, 1987;Grondin, 1991a, 1992;Castle, 1990;Goncz et al, 1995). The regulatory processes of the exocytotic mechanism may vary among different cells as well as the mechanism of fusion of the granule membrane with the apical plasma membrane.…”