The v-SNARE (synaptobrevin), which are incorporated into the

The
cell membrane is a biological membrane that
consists of a lipid bilayer which separates the interior of all cells from the outside environment. It is associated
with several cellular processes including cell signaling,
exocytosis, membrane fusion, and ion conductance (Jahn et al., 2003; Jing et al
2017). Exocytosis is an essential membrane process in which the intracellular vesicles fuse with the
plasma membrane and release their contents (proteins, hormones or
neurotransmitters) to allow for exchange or
compartmentalization of molecules (Jahn et al., 2003; Chernomordik and Kozlov,
2005). Exocytosis is involved in several
cellular events including the release of neurotransmitters from presynaptic
neurons in synaptic vesicles, the release of peptide hormones from endocrine
cells and the release of mediators from mast and enterochromaffin-like cells (Chen
et al 2004).

The cycle of vesicle fusion and release of components is
driven by SNARE proteins (Jahn et al., 2003; Jing et al 2017). The SNARE proteins
are a large protein superfamily consisting of more than 60 members in both mammalian
and yeast cells. They are
involved the fusion of vesicles with membranes by forming bundle of alpha
helices. SNARE’s
can be divided into two types: vesicle-associated v-SNARE (synaptobrevin), which are incorporated into the
membranes of transport vesicles, and target
cell-associated t-SNAREs (syntaxin and SNAP-25) which are associated with nerve terminal membranes (Kloepper et al.,
2007; Jing et al 2017).

Exocytosis is a complex process consisting of a series of distinct steps.
The first step is docking in which the synaptic vesicle and the plasma membrane
are brought into contact and line
up in a fusion-ready state. Although SNARE proteins paly an important role in
mediating exocytosis, experimental studies suggest that SNARE
proteins are not involved in the docking process (Koeppen et al 2017, Jing
et al 2017).

Following docking, vesicles must be primed in order to
maintain a repaid fusion in response to calcium influx. This priming step
starts with the formation of SNARE complexes by combining the ?-helix domains from synaptobrevin, syntaxin, and SNAP-25 and form a coiled-coil motif. However,
the
t-SNARE syntaxin is usually
found in a closed state which prevents it from interacting with other SNARE
proteins. Several proteins including UNC-13 and Rim participate in stimulating
the change of t-SNARE from a closed state into an open state and stimulates the
assembly of v-SNARE/t-SNARE complexes (Koeppen et al 2017). Pairing of the
SNAREs brings the membranes into close proximity and leads to the merger of
both membranes. Later, primed vesicles fuse very quickly in
response to calcium elevations in the cytoplasm. This fusion event is thought
to be mediated directly by SNAREs and driven by the energy provided from SNARE complex
assembly. Calcium ions binds to synaptotagmin and Ca++-synaptotagmin complex
binds to SNAREs and imbeds into plasma membrane (Koeppen et al 2017). In the
final step, synaptic vesicle proteins now have been
incorporated into the plasma membrane and the neurotransmitter or hormone is
released.

There are several features of SNARE proteins
that are significant in exocytosis and membrane fusion process. The SNARE complex is highly stable and it provides an
important energy source for the fusion process to be completed. Moreover, the
SNARE complex is consisted of at least two SNARE molecules with domains that
helps in membrane fusion. Last, SNARE’s assemble in a parallel orientation which
leads to the close apposition of the membranes (Parlati et al 2000; Langosch et
al 2007).