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Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The SNARE complex is formed by members of the synaptosomal-associated protein 25 (SNAP-25), vesicle-associated membrane protein (VAMP) and members of the syntaxins family. Interactions between these proteins create a four-helix bundle, formed by two helices of SNAP-25, one vesicular-transmembrane VAMP and one presynaptic plasma membrane syntaxin that brings together the vesicular and plasmatic membranes. Other proteins that interact with the SNARE complex include Munc-18, complexin, synaptophysin, and synaptotagmin [77]. In addition, synaptotagmin serves as a calcium sensor and regulates the SNARE zipping. The SM proteins are evolutionary conserved cytosolic proteins that serve as essential partners for SNARE proteins in fusion. Among these is Munc 18, which primarily interacts with syntaxin-1 and whose function is tightly regulated by calcium.
Recurrence of endometriosis
Published in Seema Chopra, Endometriosis, 2020
The CA-125, IL 8, TNF-α combination showed a sensitivity of 89.7% and a specificity of 71% [19]. The CA-125, laminin 1, syntaxin 5 combination was studied by Ozhan et al. [20] and found 90% sensitivity and 70% specificity. A CA-125, CA 19-9, CA 15-3 panel was found to be increased in the endometrium and area under the curve was highest for CA-125 [21]. The panel of CA-125, annexin V, vascular endothelial growth factor, and soluble intercellular adhesion molecule (sICAM1) showed a specificity of 55%–75% and a sensitivity of 74%–99% but needs further prospective trials [22].
Primary immunodeficiency diseases
Published in Gabriel Virella, Medical Immunology, 2019
John W. Sleasman, Gabriel Virella
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder due to impaired lymphocyte cytotoxic activity due to defective formation of the immunologic cell-to-cell synapse that enables cytotoxic T cells and NK cells to kill an infected cellular target. The result is massive abnormal activation of T cells and macrophages, overproduction of γ-interferon, and infiltration of activated macrophages in the liver, bone marrow, spleen, and the central nervous system with massive hemophagocytosis. Clinical criteria include high fever with splenomegaly, autoimmune thrombocytopenia, neutropenia, and hemolytic anemia, and histologic evidence of hemophagocytosis in the tissues. Immune activation markers such as very high ferritin levels, hypofibrinogenemia, hyperlipidemia, and elevated plasma levels of soluble IL-2 receptor (sCD25) are usually found. Low NK numbers and activity are common. Familial forms can first appear in infancy or later in life and enable infection with human herpes viruses, particularly EBV. Mutations in Perforin, Syntaxin 11, and Munc 18 are the most common known genetic forms as all of these proteins play a critical role in tethering and formation of the immunologic synapse.
Neonatal platelet physiology and implications for transfusion
Published in Platelets, 2022
Francisca Ferrer-Marín, Martha Sola-Visner
P-selectin translocates from α-granules to the platelet surface membrane following platelet activation. Interestingly, although both human and murine neonatal platelets show decreased surface P-selectin expression upon activation compared to adult platelets, the total P-selectin content is developmentally reduced in platelets from newborn mice [21,22] but not in platelets from human neonates [7]. In regard to granule content, ultrastructural studies have shown that whereas the number of dense granules in human neonatal platelets is lower than in adult platelets[23], the number of α-granules, which are the most abundant, is similar [7,23–25]. The reduced exocytosis of α-granules in CB-derived platelets is associated with a lower expression of β1-tubulin (required for granule centralization) and of Syntaxin-11/Munc18b complex and VAMP7 (SNARE proteins required for the fusion of vesicles to plasma membranes)[7]. As a result, neonatal platelet spreading is reduced and delayed both in humans (in plasma-free conditions) [7] and in mice[21].
The role of synaptic biomarkers in the spectrum of neurodegenerative diseases
Published in Expert Review of Proteomics, 2020
Sonia Mazzucchi, Giovanni Palermo, Nicole Campese, Alessandro Galgani, Alessandra Della Vecchia, Andrea Vergallo, Gabriele Siciliano, Roberto Ceravolo, Harald Hampel, Filippo Baldacci
SNAP-25 is a SNARE protein located in the pre-synaptic terminals, which is essential for docking and fusion of exocytic vesicles to the plasma membrane. Together with syntaxin-1 and vesicle-associated membrane protein 2 (VAMP2)/synaptobrevin, SNAP-25 is one of the major proteins involved in the complex molecular machinery that drives the fusion of membranes in neurotransmitter release [87]. Additionally, it modulates calcium dynamics in response to depolarization, representing an important marker of functional synapses, and has also been implicated in axonal outgrowth and neurite elongation [9,88]. The SNAP-25 gene is highly expressed in hippocampal neurons, suggesting its crucial role in memory processes and learning [10]. Accordingly, SNAP-25 single nucleotide polymorphisms have been associated with cognitive decline [89]. Alterations in SNAP-25 expression were demonstrated also in non-NDD such as psychiatric and autoimmune disorders [90–93].
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.