Neuronal Porosome Complex: Secretory Machinery at the Nerve Terminal.

Mzia G Zhvania,Nino Pochkidze

doi:10.15190/d.2017.7

Abstract

Neuronal porosomes are 15 nm cup-shaped lipoprotein secretory machines composed of nearly 30 proteins present at the presynaptic membrane, that have been investigated using multiple imaging modalities, such as electron microscopy, atomic force microscopy, and solution X-ray. Synaptic vesicles transiently dock and fuse at the base of the porosome cup facing the cytosol, by establishing a fusion pore for neurotransmitter release. Studies on the morphology, dynamics, isolation, composition, and reconstitution of the neuronal porosome complex provide a molecular understanding of its structure and function. In the past twenty years, a large body of evidence has accumulated on the involvement of the neuronal porosome proteins in neurotransmission and various neurological disorders. In light of these findings, this review briefly summarizes our current understanding of the neuronal porosome complex, the secretory nanomachine at the nerve terminal.

Highlights

Porosomes are cup-shaped secretory nanomachines at the plasma membrane of all cells, including neurons (Figure 1), observed using electron microscopy, atomic force microscopy, and solution X-ray, that allow for the precise docking, transient fusion, and fractional release of intravesicular contents from cells[1,2,3,4,5,6,7,8,9,10,11,12] during secretion
Following discovery of the v-SNARE and t-SNARE proteins[25,26,27] and the establishment of their role in membrane fusion in cells[28], it was hypothesized that both SNAREs in opposing lipid membrane interact in a rosette or ring configuration[28]
This hypothesis was confirmed for the first time in an elegant 2002 study[16], using membrane associated full length recombinant t- and v-SNAREs and nanometer scale imaging using atomic force microscopy[16]

Summary

Introduction

Porosomes are cup-shaped secretory nanomachines at the plasma membrane of all cells, including neurons (Figure 1), observed using electron microscopy, atomic force microscopy, and solution X-ray, that allow for the precise docking, transient fusion, and fractional release of intravesicular contents from cells[1,2,3,4,5,6,7,8,9,10,11,12] during secretion. Porosome proteins reticulons contribute to lipid membrane curvature and diseases associated with their deregulation adversely affect neurotransmitter release These are just a few examples of neuronal porosome proteins that have been implicated both in neurotransmission and in their altered states in neurological disorders. Following discovery of the v-SNARE and t-SNARE proteins[25,26,27] and the establishment of their role in membrane fusion in cells[28], it was hypothesized that both SNAREs in opposing lipid membrane interact in a rosette or ring configuration[28] This hypothesis was confirmed for the first time in an elegant 2002 study[16], using membrane associated full length recombinant t- and v-SNAREs and nanometer scale imaging using atomic force microscopy[16]. Greater the secretory vesicle size, larger is the size of the SNARE rosette complex[17,20,21]

Synaptic vesicle volume regulation in neurotransmission

Conclusion