Synaptotagmins: Beyond Presynaptic Neurotransmitter Release

Wu, Xuanang; Hu, Shaoqin; Kang, Xinjiang; Wang, Changhe

doi:10.1177/1073858419844497

Cited by 18 publications

(19 citation statements)

References 41 publications

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“…This result could be explained with the ability of this compound to restore the physiological values of expression of selected proteins. The three proteins taken into consideration, namely Syt 1, Stx 1b and CAMK2A, are notoriously involved in neurotransmitter exocytosis from ready releasable vesicles and in synaptic plasticity [43,44]. The 5-HT pathway has also been considered as cornerstone to explain the antidepressant effects in mice treated with CBD [45].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Giacomo

Chiavaroli

Recinella

et al. 2020

IJMS

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Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.

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Section: Discussionmentioning

confidence: 99%

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Giacomo

Chiavaroli

Recinella

et al. 2020

IJMS

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“…SYT12 was first described as being homologous to SYT1, which is a thyroid hormone-induced protein [7]. The synaptotagmins, including SYT1, were identified in 1990 [20], and have been established as the primary Ca 2+ sensors for vesicular exocytosis and endocytosis [6]. Mammalian cells contain 17 genes that encode synaptotagmins, and all 17 synaptotagmins have similar molecular structures, but only a minority have been studied in detail [6].…”

Section: Discussionmentioning

confidence: 99%

“…The synaptotagmins, including SYT1, were identified in 1990 [20], and have been established as the primary Ca 2+ sensors for vesicular exocytosis and endocytosis [6]. Mammalian cells contain 17 genes that encode synaptotagmins, and all 17 synaptotagmins have similar molecular structures, but only a minority have been studied in detail [6]. Few previous studies have reported the association between synaptotagmin family members and human cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The nude mice were divided equally into six groups. After transfection, 2×10 6 LUAD cells in 100 μl of sterile PBS were injected subcutaneously into each mouse. The tumors were harvested six weeks after injection.…”

Section: Luad Tumor Xenografts In Nude Micementioning

confidence: 99%

“…SYT12 is a member of synaptotagmins family. Synaptotagmins are membrane proteins which compose of a short N-terminal non-cytoplasmic sequence, a transmembrane region, a linker sequence with variable length, and two C2-domains [6]. In 1996, Thompson initially reported that the expression of the SYT12 protein was induced by thyroid hormone and was homologous to SYT1 but without Ca 2+ -binding sequences [7].…”

Section: Introductionmentioning

confidence: 99%

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Synaptotagmin 12 (SYT12) Gene Expression Promotes Cell Proliferation and Progression of Lung Adenocarcinoma and Involves the Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway

et al. 2020

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Background: This study aimed to use bioinformatics analysis to compare data from tissue microarrays from patients with lung adenocarcinoma (LUAD) and normal lung tissue, and human lung adenocarcinoma cells with normal lung epithelial cells in vitro to investigate the role of synaptotagmin 12 (SYT12) gene expression in LUAD. Material/Methods: Human lung adenocarcinoma cell lines (A549, SPC-A-1, H1299, H1975, and PC9) and the normal HBE cell line were compared, and tumor xenografts were developed in mice. The Cancer Genome Atlas (TCGA) tissue microarray data were used to compare SYT12 expression and overall survival (OS). The in vivo and in vitro effects of down-regulation and upregulation of SYT12 were studied using short-interfering RNA (si-RNA) and overexpression plasmids, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and Western blot investigated the molecular mechanisms of SYT12 expression in LUAD. Results: SYT12 expression was increased in tissues from patients with LUAD from TCGA and was associated with advanced tumor stage and reduced prognosis. Knockdown of SYT12 suppressed the proliferation and migration of LUAD cells, and upregulation of SYT12 increased the proliferation and migration of LUAD cells in vitro. Phosphorylation of PIK3R3 activated the PI3K/AKT/mTOR pathway. In the mouse xenograft model, expression of SYT12 increased the volume and weight of the xenograft tumors. Conclusions: Bioinformatics analysis, human LUAD cells, and mouse xenograft studies showed that SYT12 acted as a possible oncogene by phosphorylation of PIK3R3 to activate the PI3K/AKT/mTOR signaling pathway.

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Function of Drosophila Synaptotagmins in membrane trafficking at synapses

Quiñones-Frías

Littleton

2021

Cell. Mol. Life Sci.

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The Synaptotagmin (SYT) family of proteins play key roles in regulating membrane trafficking at neuronal synapses. Using both Ca2+-dependent and Ca2+-independent interactions, several SYT isoforms participate in synchronous and asynchronous fusion of synaptic vesicles (SVs) while preventing spontaneous release that occurs in the absence of stimulation. Changes in the function or abundance of the SYT1 and SYT7 isoforms alter the number and route by which SVs fuse at nerve terminals. Several SYT family members also regulate trafficking of other subcellular organelles at synapses, including dense core vesicles (DCV), exosomes, and postsynaptic vesicles. Although SYTs are linked to trafficking of multiple classes of synaptic membrane compartments, how and when they interact with lipids, the SNARE machinery and other release effectors are still being elucidated. Given mutations in the SYT family cause disorders in both the central and peripheral nervous system in humans, ongoing efforts are defining how these proteins regulate vesicle trafficking within distinct neuronal compartments. Here, we review the Drosophila SYT family and examine their role in synaptic communication. Studies in this invertebrate model have revealed key similarities and several differences with the predicted activity of their mammalian counterparts. In addition, we highlight the remaining areas of uncertainty in the field and describe outstanding questions on how the SYT family regulates membrane trafficking at nerve terminals.

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Synaptotagmins: Beyond Presynaptic Neurotransmitter Release

Cited by 18 publications

References 41 publications

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Synaptotagmin 12 (SYT12) Gene Expression Promotes Cell Proliferation and Progression of Lung Adenocarcinoma and Involves the Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway

Function of Drosophila Synaptotagmins in membrane trafficking at synapses

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