Role in neurotransmitter release::SNARE (protein)


Journal::snare    Membrane::fusion    Title::volume    Pages::proteins    Complex::snap-    Issue::vauthors

Role in neurotransmitter release Neurotransmitters are stored in readily releasable pools of vesicles confined within the presynaptic terminal. During neurosecretion/exocytosis, SNAREs play a crucial role in vesicle docking, priming, fusion, and synchronization of neurotransmitter release into the synaptic cleft.

The first step in synaptic vesicle fusion is tethering, where the vesicles are translocated from the reserve pool into physical contact with the membrane. At the membrane, Munc-18 is initially bound to syntaxin 1A in a closed structure. It is postulated that the dissociation of Munc-18 from the complex frees syntaxin 1A to bind with the v-SNARE proteins.<ref>{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref> The next step in release is the docking of vesicles, where the v- and t-SNARE proteins transiently associate in a calcium-independent manner. The vesicles are then primed, wherein the SNARE motifs form a stable interaction between the vesicle and membrane. Complexins stabilize the primed SNARE-complex rendering the vesicles ready for rapid exocytosis.

The span of presynaptic membrane containing the primed vesicles and dense collection of SNARE proteins is referred to as the active zone. Voltage-gated calcium channels are highly concentrated around active zones and open in response to membrane depolarization at the synapse. The influx of calcium is sensed by synaptotagmin 1, which in turn dislodges complexin protein and allows the vesicle to fuse with the presynaptic membrane to release neurotransmitter. It has also been shown that the voltage-gated calcium channels directly interact with the t-SNAREs syntaxin 1A and SNAP-25, as well as with synaptotagmin 1. The interactions are able to inhibit calcium channel activity as well as tightly aggregate the molecules around the release site.<ref name = "Ramakrishnan_2012">{{#invoke:Citation/CS1|citation |CitationClass=journal }}</ref>

There have been many clinical cases that link SNARE genes with neural disorders. Deficiency in SNAP-25 mRNA has been observed in hippocampal tissue of some schizophrenic patients, a SNAP-25 single-nucleotide polymorphism is linked to hyperactivity in autism-spectrum disorders, and overexpression of SNAP-25B leads to the early onset of bipolar disorder.<ref name = "Ramakrishnan_2012"/>

SNARE (protein) sections
Intro   Types    Structure    Membrane fusion    Components    Mechanism of membrane fusion   Regulatory Effects on Exocytosis   Toxins    Role in neurotransmitter release    Role in autophagy   References  External links  

Role in neurotransmitter release