Ångstrom-size exocytotic fusion pore: Implications for pituitary hormone secretion. (5th March 2018)

• Record Type: Journal Article
• Authors: Kreft, Marko; Jorgačevski, Jernej; Stenovec, Matjaž; Zorec, Robert
• Is Part Of: Molecular and cellular endocrinology. Volume 463(2018)
• Page Start: 65
• Page End: 71
• Publication Date: 2018-03-05
• Subjects: Regulated exocytosis -- Fusion pore -- Fusion pore stability -- Membrane capacitance; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.04.023
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: In the past, vesicle content release was thought to occur immediately and completely after triggering of exocytosis. However, vesicles may merge with the plasma membrane to form an Ångstrom diameter fusion pore that prevents the exit of secretions from the vesicle lumen. The advantage of such a narrow pore is to minimize the delay between the trigger and the release. Instead of stimulating a sequence of processes, leading to vesicle merger with the plasma membrane and a formation of a fusion pore, the stimulus only widens the pre-established fusion pore. The fusion pore may be stable and may exhibit repetitive opening of the vesicle lumen to the cell exterior accompanied by a content discharge. Such release of vesicle content is partial (subquantal), and depends on fusion pore open time, diameter and the diffusibility of the cargo. Such transient mode of fusion pore opening was not confirmed until the development of the membrane capacitance patch-clamp technique, which enables high-resolution measurement of changes in membrane surface area. It allows millisecond dwell-time measurements of fusion pores with subnanometer diameters. Currently, the soluble N -ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) proteins are considered to be key entities in end-stage exocytosis, and the SNARE complex assembly/disassembly may regulate the fusion pore. Moreover, lipids or other membrane constituents with anisotropic (non-axisymmetric) geometry may also favour the establishment of stable narrow fusion pores, if positioned in the neck of the fusion pore. Graphical abstract: Highlights: The vesicle and plasma membranes may merge to form an Ångstrom diameter fusion pore. The narrow fusion pore may hinder passage of large vesicle cargo molecules. The narrow fusion pore may exhibit repetitive opening. Anisotropic lipids may favour the establishment of stable fusion pores.