Homeostasis of Dopamine
Nira Ben-Jonathan in Dopamine, 2020
The span of presynaptic membrane that contains the primed vesicles and the dense collection of SNARE proteins is referred to as the active zone. Voltage-gated calcium channels are highly concentrated around the 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 the complexin protein and allows the vesicle to fuse with the presynaptic membrane and release the 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. During exocytosis, v-SNAREs (e, g., synaptobrevin) and t-SNAREs (e.g., syntaxin and SNAP-25) assemble into a core trans-SNARE complex. This complex plays multiple roles during the various stages of exocytosis, including priming, fusion, pore formation, and expansion, eventually resulting in the release of the vesicle content.
Cognitive Functions, Attention-Deficit Hyperactivity Disorders, and Alzheimer’s Disease
Divya Vohora in The Third Histamine Receptor, 2008
Meta-analyses have also implicated polymorphisms in the genes coding for SNAP-25 (a presynaptic plasma membrane protein with an integral role in synaptic transmission) and the serotonin transporter with ADHD. SNAP-25 forms a complex with syntaxin 1a and synaptic vesicle proteins such as VAMP-2 (synaptobrevin 2) and synaptotagmin, which mediates calcium-dependent exocytosis of neurotransmitter from the synaptic vesicle into the synaptic cleft [16]. High levels of SNAP-25 have been found in regions such as the hippocampus, neocortex, thalamus, substantia nigra, and cerebellum. In a recent study of 93 ADHD nuclear families in Ireland, significant increased preferential transmission of the SNAP-25 polymorphism Ddel allele 1 was found [17]. In a separate study of Canadian families with ADHD, significant increased preferential transmission of the SNAP-25 polymorphism Ddel allele 2 was found [18]. Additional haplotype analysis of SNAP-25 implicates SNAP-25 in the etiology of ADHD.
Physiological Properties of the Lower Urinary Tract
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Addition of cytoplasmic vesicles into the apical membrane during bladder filling and their removal during contraction (6,7) minimizes the surface to volume ratio of the bladder and hence the flux of substances over the urothelium. Recent studies have shown that stretch to either apical or basolateral membrane exerts opposite effects (8). Stretch also increases protein secretion into the urine, raises cell cAMP levels (7), and stimulates ATP release into the blood side (9) (the latter is also considered in section “Secretory and Signaling Properties of the Urothelium/Suburothelium”). Release of ATP results in its binding to purinergic (P2X) receptors on the basolateral membrane of the apical cells and stimulates an increase in the intracellular [Ca2+], [Ca2+]j, which in turn stimulates vesicle fusion (7,10). Raised [Ca2+]j is also induced by capsaicin and blocked by the vanilloid receptor antagonists. The molecular basis of vesicle fusion shares many features with synaptic vesicle fusion. The apical membrane and the fusiform/discoidal vesicles contain SNAP 23 and SNARES—synaptobrevin and syntaxin. Another key component for synaptic vesicle fusion is the Rab proteins, with Rab 27b found in umbrella cells (11).
Nanobodies reveal an extra-synaptic population of SNAP-25 and Syntaxin 1A in hippocampal neurons
Published in mAbs, 2019
Manuel Maidorn, Aurélien Olichon, Silvio O. Rizzoli, Felipe Opazo
Here we present two novel nanobodies that were selected and produced to detect the synaptic proteins SNAP-25 and Syntaxin 1A with high specificity and affinity. Syntaxin 1A is one of two isoforms of this molecule expressed in the nervous system. These isoforms (1A and 1B) show overlapping, albeit not identical, distributions,21,22 similar functions,23 and similar levels in central nervous system synapses.5 Using nanobodies for SNAP-25 and Syntaxin 1A, we could reproduce some of the previously published results on the distribution of these molecules in neurons, although the staining pattern presented by the nanobody suggested a far smoother staining than the one obtained by antibodies. Interestingly, the nanobodies also revealed large populations of both SNAP-25 and Syntaxin 1A outside the synapses, which were poorly revealed by the antibodies. Furthermore, the extra-synaptic Syntaxin 1A molecules, but not the SNAP-25 molecules, were recruited to the synaptic boutons center upon strong neuronal stimulation. In addition, two-color investigations using super-resolution microscopy also showed that the SNAP-25 and Syntaxin 1A are better correlated than previous antibody-based measurements have suggested both within and outside synapses. Overall, these findings suggest that small, monovalent probes such as nanobodies are able to detect not only quantitative, but also qualitative differences in molecular distribution, when compared to antibodies.
Postsynaptic Syntaxin 4 negatively regulates the efficiency of neurotransmitter release
Published in Journal of Neurogenetics, 2018
Kathryn P. Harris, J. Troy Littleton, Bryan A. Stewart
Syntaxin 4 regulates multiple aspects of synaptic biology. Here we report a that loss of Syx4 leads to synaptic enhancement, a surprising finding give that Syx4 mutant synapses have significantly fewer active zones than the control animals. We observed an increase in evoked release, and a reduction in paired-pulse facilitation, in Syx4 mutants. We also identified two mechanisms that are likely to contribute to the increase in neurotransmission: an increase in the levels of the presynaptic Ca2+ channel Cac at individual active zones, and a decrease in Ca2+ cooperativity. These two potentiation mechanisms could be linked – for example, an increase in Cac channels, leading to changes in Ca2+ influx and the spatial arrangement of the channels, could contribute to changes in the sensitivity of the exocytotic machinery to Ca2+. However, we cannot rule out the possibility that they are distinct phenomena. As all of these phenotypes are rescued by postsynaptic, but not presynaptic, expression of Syx4, our data indicate a retrograde signaling mechanism by which Syx4 regulates active zones.
Effects of spontaneous recurrent seizures on cognitive function via modulation of SNAREs expression
Published in International Journal of Neuroscience, 2018
Hua Yu, Xuelian Yang, Xu Tang, Renkuan Tang
The pathogenesis of epilepsy is complex and is influenced by numerous factors, of which neurotransmitter and synaptic transmission are the most important [12,13]. The process of synaptic transmission is mainly regulated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complexes that play important roles in synaptic vesicle fusion and neurotransmitter release [14–16]. Exocytosis is driven by the interactions among syntaxin-1 (Syt-1), SNAP-25 on the plasma membrane and synaptobrevin-2 (Syp) protein on the vesicle membrane, which component the SNARE complexes [17]. The SNARE complexes may play an important and diverse role in developmental disorders, especially on cognitive function such as attention and memory [18,19]. They also participate in calcium-dependent exocytosis of synaptic vesicles, ensuring effective release of neurotransmitters and action potential conduction [20]. They are also important for learning, movement, memory formation and normal brain function [21].
Related Knowledge Centers
- Protein
- Snare Protein
- Synapse
- Synaptic Vesicle
- Synaptobrevin
- Synaptotagmin
- Cell Membrane
- Exocytosis
- Snap25
- Munc-18