Homeostasis of Dopamine
Nira Ben-Jonathan in 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.
Skeletal Muscle
Manoj Ramachandran, Tom Nunn in Basic Orthopaedic Sciences, 2018
In the motor neuron, depolarization at the axon terminal produces an influx of Ca2+ through N-type voltage-sensitive channels. Increased concentrations of intracellular Ca2+ are believed to act through binding synaptotagmin, leading to fusion of preformed vesicles containing acetylcholine (ACh) with the pre-synaptic membrane. Acetylcholine released into the synaptic cleft binds to post-synaptic nicotinic ACh receptors (nAChR) on the sarcolemma (Figure 12.5). The nAChR is a non-specific monovalent cation channel, opened by binding ACh. The resulting Na+ influx causes depolarization of the muscle fibre membrane known as the end-plate potential.
Pharmacotherapy of Neurochemical Imbalances
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Other molecule which is able to bind Ca2+ is the phosphatase calcineurin that is a serine/threonine phosphatase. Occupation of the calcium-binding site makes a structural change that exposes a Ca2+-CaM binding site. Once Ca2+-CaM binds to a subunit, it becomes active, dephosphorylation a number of intracellular targets. Exocytosis process of neurotransmitter release from synaptic vesicles is known to be mediated via Synaptotagmin present in all neurons (Claudia and Fabiola, 2014).
The neurosciences at the Max Planck Institute for Biophysical Chemistry in Göttingen
Published in Journal of the History of the Neurosciences, 2023
The Max Planck Society, unfortunately, could not offer Jahn an adequate position after his post as head of the Junior Investigators Group in Munich expired, and he returned to the United States. There, he was at the Yale University School of Medicine from 1991 to 1997, his last position being professor of pharmacology and cell biology. During this time, he made important contributions toward identifying synaptotagmin (previously P65) as a Ca2+ sensor in the release of neurotransmitters (Brose et al. 1992). He was also able to demonstrate how neurotoxins like tetanus toxin or botulinum toxin inhibit the release of neurotransmitters by interacting with synaptobrevin, syntaxin, or SNAP 25 (Blasi et al. 1993). In 1995, Jahn was appointed a scientific member and director of the Department for Neurobiology at the MPI for Biophysical Chemistry, taking up his work in Göttingen in 1997.25Reinhard Jahn was appointed to the MPI for Biophysical Chemistry as a scientific member and director on March 24, 1995, in the first round and on June 22, 1995, in the second round by the Senate of the Max Planck Society. See the minutes of the 139th session of the Senate from March 24, 1995, in Berlin, AMPG, II. Abt., Rep. 60, Nr. 139, as well as the minutes of the 140th session of the Senate from June 22, 1995, in Potsdam, AMPG, II. Abt., Rep. 60, Nr. 140.
Marinoid J, a phenylglycoside from Avicennia marina fruit, ameliorates cognitive impairment in rat vascular dementia: a quantitative iTRAQ proteomic study
Published in Pharmaceutical Biology, 2020
Xiang-xi Yi, Jia-yi Li, Zhen-zhou Tang, Shu Jiang, Yong-hong Liu, Jia-gang Deng, Cheng-hai Gao
Signal transmission at the neuromuscular junction is mediated via the release of acetylcholine from synaptic vesicles. This process is rendered calcium-sensitive by members of the Synaptotagmin family, which also has roles in vesicle priming and in reducing spontaneous neurotransmitter release (Lee et al. 2008). SYT2 is the major isoform expressed at the neuromuscular junction, and previous studies have shown that Syt2 knockout mice show markedly reduced calcium-evoked neurotransmitter release (Pang et al. 2006). A previous study (Whittaker et al. 2015) found that Syt2 mutations cause a novel and potentially treatable complex presynaptic congenital myasthenic syndrome characterized by motor neuropathy inducing lower-limb wasting and foot deformities. A recent study (Bereczki et al. 2018) used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospective AD patients, PD patients with dementia, dementia patients with Lewy bodies, and older adults without dementia. They found a significant loss of SYT2, which implicates that it could be a synaptic marker of cognitive decline in neurodegenerative diseases. Our present study showed that abnormal expression of SYT2 may be related to the occurrence of VD, and PGs may decrease the expression of SYT2 in VD rats, thereby alleviating the symptoms of VD rats.
Misrouting of glucagon and stathmin-2 towards lysosomal system of α-cells in glucagon hypersecretion of diabetes
Published in Islets, 2022
Farzad Asadi, Savita Dhanvantari
The decrease in high glucose-induced glucagon secretion upon BafA1 treatment indicates that glucagon secretory granules are fusing with a lysosomal compartment that is secretion-competent. Since trafficking to the Lamp2A+ lysosome is inhibited in diabetes, it is possible that glucagon is trafficked to a secretory lysosome. We used Lamp1 to identify lysosomes that might have a secretory function, as Lamp1 is found on non-degradative lysosomes, and these lysosomes are often found at the plasma membrane.46,47 In diabetes-mimicking αTC1-6 cells, Lamp1+ lysosomes appear to be distributed at the plasma membrane, together with glucagon+ secretory granules. Co-localization of Lamp1 and glucagon at the plasma membrane suggests some degree of fusion of secretory granules with Lamp1+ lysosomes. Membrane-adjacent Lamp1+ vesicles contain the Ca2+-sensitive SNARE protein synaptotagmin 7 in MIN6 and INS1E cells,48 and may play a role as a Ca2+ sensor in lysosomal fusion and exocytosis. It is known that that the SNARE proteins VAMP7, SNAP23 and syntaxin 4 function in lysosomal fusion and exocytosis.49 Therefore, regulated exocytosis via lysosomes, in addition to enhanced secretory granule exocytosis, may contribute to the up-regulation of glucagon secretion in diabetes. It has been documented that mutant huntington is secreted via Lamp1+ lysosomes in a synaptotagmin 7-dependent manner.50 Although we did not show such a mechanism in the present study, the role of secretory lysosomes in hyperglucagonemia will be the subject of future studies.