A trans-membrane pore can account for protein movement across zymogen granule membranes

We have reported that the membrane of zymogen granules, secretion vesicles from the exocrine pancreas, is permeable to its contained proteins by measuring both the loss and accumulation of protein in response to mass action forces [1-3] However, the mechanism of transport has remained unknown. Here we consider evidence that this transport occurs through trans-membrane pores. Using freeze-fracture electron microscopic methods, Cabana et al. [4] have reported the presence of a 15 nm intramembrane particle in zymogen granule membrane which contains a 5 nm (+/- 0.1 nm, S.D.) diameter lucent center. In this article, we propose that this structure is a pore through which proteins can be transported, and test this hypothesis by comparing the predicted phenomenological permeability coefficient for transport by diffusion via this structure, to that calculated from protein flux measurements on granules using an X-ray microscope. The predicted and experimental values were essentially identical and hence support the hypothesis that this structure could be a protein transporting channel.