Porosomes: Supramolecular structures at the synaptosome membrane involved in vesicle docking, fusion, and neurotransmitter release

Abstract

Cup-shaped supramolecular structures at the cell plasma membrane called porosomes mediate the fractional discharge of vesicular contents from cells during secretion. Membrane-bound secretory vesicles transiently dock and fuse at the porosome base via SNARE proteins, to expel vesicular contents to the outside during cell secretion. Porosomes range in size from 15 nm in neurons and astrocytes to 180 nm in endocrine and exocrine cells. Neuronal porosomes are composed of nearly 40 proteins, compared to the 120 nm nuclear pore composed of nearly 1000 protein molecules. Determination of the presence of porosomes in all cells examined and an understanding of their structure, composition, and functional reconstitution into artificial lipid membrane and in live cells provide a molecular understanding of cell secretion. In this chapter, the discovery and structural characterization of the neuronal porosome at the synaptosome membrane using atomic force microscopy, electron microscopy, and small-angle X-ray solution scattering; its isolation and both structural and functional reconstitution into artificial lipid membrane; and the possible molecular mechanism of its involvement in neurotransmitter release are presented. The assembly of neuronal t/v-SNARE complexes in a rosette or ring when t-SNAREs (present at the porosome base) in one membrane interact with v-SNAREs (secretory vesicle) in an opposing membrane and the molecular mechanism of synaptic vesicle swelling required for the regulated fractional release of vesicle contents are also presented in this chapter.