Abstract

A major question in cell biology that accumulation of partially empty vesicles in cells following secretion is seen, while it is believed that secretion occurs via the complete merger of secretory vesicles with the cell plasma membrane. This important question was solved nearly two decades ago, with the discovery of the Porosome. Porosomes are cup-shaped lipoprotein structures found at the plasma membrane of all cells. Secretory vesicles dock and transiently fuse at the porosome base to form a continuous channel or fusion pore to release the pressurized vesicle contents to the outside. In a decade-long study by our group, we carefully examined using electron microscopy, the detailed structure of the porosome complex in acinar cells of the exocrine pancreas. Besides conformation of earlier findings, our study provides in much greater detail, the in situ morphology of the porosome complex in the exocrine pancreas. The discovery of the detailed morphology of the exocrine pancreas porosome complex in my laboratory is one of the major highlights of my academic career spanning nearly 50 years. Results from our EM studies, reveal for the first time the presence of tethers or cables, which are likely t-SNAREs, present at the porosome base. These EM studies further demonstrate for the first time the docking of a single secretory vesicle or zymogen granule at the base of more than one porosome complex. Detailed spoke-like elements lining the porosome cup were also observed for the first time in these studies, greatly advancing our understanding of the molecular architecture and physiology of the porosome in the exocrine pancreas.

Highlights

  • In the first January 1997 issue of the Proceedings of the National Academy of Sciences of the United States of America[1], a breakthrough in our understanding of live cell structure-function at nanometer resolution, using a new technology of atomic force microscopy, was reported

  • The POROSOME is a docking station for secretory vesicles, controlling and modulating the release of their pressurized contents to the outside structure ‘the porosome’ was discovered, and determined to participate in the important cellular process of secretion. It solved a major question in cell biology, since the accumulation of partially empty vesicles in cells following secretion was previously unexplainable due to the belief that all secretion occurs via the complete merger of secretory vesicle membrane with the cell plasma membrane[2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]

  • The porosome discovery provided the answer, demonstrating that secretory vesicles transiently fuse at the porosome base to establish a fusion pore or channel through which secretory products are released in a highly regulated manner from cells during secretion[24,25,26,27,28,29,30,31,32,33,34,35,36]

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Summary

Introduction

In the first January 1997 issue of the Proceedings of the National Academy of Sciences of the United States of America[1], a breakthrough in our understanding of live cell structure-function at nanometer resolution, using a new technology of atomic force microscopy, was reported. The porosome discovery provided the answer, demonstrating that secretory vesicles transiently fuse at the porosome base to establish a fusion pore or channel through which secretory products are released in a highly regulated manner from cells during secretion[24,25,26,27,28,29,30,31,32,33,34,35,36]. B. Jena and his research team have discovered a new cellular structure, the ‘porosome’, located at the cell plasma membrane, where secretory vesicles fuse to release their cargo.

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