Neuronal porosome proteome: Molecular dynamics and architecture

Porosomes are the universal secretory portals at the cell plasma membrane, where membrane-bound secretory vesicles transiently dock and fuse to expel intravesicular contents to the outside during cell secretion. In the past decade, the neuronal porosome complex, a 10–15 nm cup-shaped lipoprotein structure has been isolated, its partial composition and 3D contour map determined, and it has been functionally reconstituted into artificial lipid membrane. Here we further determine the composition of the neuronal porosome proteome using immunoisolation and gel filtration chromatography, followed by tandem mass spectrometry. Results from the study demonstrate nearly 40 proteins to constitute the neuronal porosome proteome. Furthermore, interaction of proteins within the porosome and their resulting arrangement is predicted. The association and dissociation of proteins at the porosome following stimulation of cell secretion demonstrate the dynamic nature of the organelle.

Graphical abstractSchematic drawing of neuronal porosome with docked synaptic vesicle. Distribution of key proteins within the 10–15 nm cup-shaped porosome is obtained from experimental results and evidence view of predicted interactions.Figure optionsDownload full-size imageDownload high-quality image (272 K)Download as PowerPoint slideHighlights► Porosomes are universal secretory portals in cells. ► Here we determine the composition of the neuronal porosome proteome. ► Molecular architecture and dynamics of the neuronal porosome are also reported.