Mechanism of secretory granule exocytosis: Can granule enlargement precede pore formation?

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Abstract
Secretory granules have been observed to swell during the process of exocytosis. Swelling is an indication of osmotic stress. The probable role of osmotic pressure in facilitating membrane fusion makes it necessary to determine whether granule membrane ‘swelling’ can occur prior to its fusion with the plasma membrane (pore formation) in the process of exocytosis. By subjecting adjacent thin and semi-thin sections of an activated granule to ultrastructural examination for membrane enlargement, and to metachromatic staining for verification of pore formation it is concluded that the perigranular membrane can indeed enlarge prior to pore formation. However, the degree of membrane enlargement can far exceed the limit of 2–3% stretching allowed under normal osmotic stress for a membrane bilayer. Such an extensive membrane enlargement, which takes place in the mechanism of exocytosis, cannot be achieved without being accompanied by the insertion of additional membrane.

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