Synaptotagmin

Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both human and animal models. Although multiple studies have looked at transcriptional changes after social defeat stress, these studies primarily focus on bulk tissues, which might dilute important molecular signatures of social interaction in activated cells. In this study, we employed the Arc-GFP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) of resilient and susceptible animals...

Migrasomes, organelles crucial for cell communication, undergo distinct stages of nucleation, maturation, and expansion. The regulatory mechanisms of migrasome formation, particularly through biological cues, remain largely unexplored. This study reveals that calcium is essential for migrasome formation. Furthermore, we identify that Synaptotagmin-1 (Syt1), a well-known calcium sensor, is not only enriched in migrasomes but also indispensable for their formation. The calcium-binding ability of Syt1 is key to initiating migrasome formation...

BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. PURPOSE: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. METHODS: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models...

Parkinson's disease is characterized by the selective degeneration of dopamine neurons in the nigrostriatal pathway and dopamine deficiency in the striatum. The precise reasons behind the specific degeneration of these dopamine neurons remain largely elusive. Genetic investigations have identified over 20 causative PARK genes and 90 genomic risk loci associated with both familial and sporadic Parkinson's disease. Notably, several of these genes are linked to the synaptic vesicle recycling process, particularly the clathrin-mediated endocytosis pathway...

Synaptotagmin-1 (Syt-1) is a calcium sensing protein that is resident in synaptic vesicles. It is well established that Syt-1 is essential for fast and synchronous neurotransmitter release. However, the role of Ca2+ and phospholipid binding in the function of Syt-1, and ultimately in neurotransmitter release, is unclear. Here, we investigate the binding of Ca2+ to Syt-1, first in the absence of lipids, using native mass spectrometry to evaluate individual binding affinities. Syt-1 binds to one Ca2+ with a K D ∼ 45 μM...

Despite decades of intense study, the molecular basis of asynchronous neurotransmitter release remains enigmatic. Synaptotagmin (syt) 7 and Doc2 have both been proposed as Ca2+ sensors that trigger this mode of exocytosis, but conflicting findings have led to controversy. Here, we demonstrate that at excitatory mouse hippocampal synapses, Doc2α is the major Ca2+ sensor for asynchronous release, while syt7 supports this process through activity-dependent docking of synaptic vesicles. In synapses lacking Doc2α, asynchronous release after single action potentials is strongly reduced, while deleting syt7 has no effect...

BACKGROUND: Synaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer's disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD...

A large proportion of patients with chronic pain experience co-morbid anxiety. The medial prefrontal cortex (mPFC) is proposed to underlie this comorbidity, but the molecular and neuronal mechanisms are not fully understood. Here, we reported that impaired neuronal macroautophagy in the prelimbic cortical (PrL) subregion of the mPFC paralleled the occurrence of anxiety-like behaviors in rats with chronic spared nerve injury (SNI). Intriguingly, such macroautophagy impairment was mainly observed in a FOS/c-Fos+ neuronal subpopulation in the PrL...

Behavioral thresholds define the lowest stimulus intensities sufficient to elicit a behavioral response. Establishment of baseline behavioral thresholds during development is critical for proper responses throughout the animal's life. Despite the relevance of such innate thresholds, the molecular mechanisms critical to establishing behavioral thresholds during development are not well understood. The acoustic startle response is a conserved behavior whose threshold is established during development yet is subsequently acutely regulated...

Biomarkers are measured to evaluate physiological and pathological processes as well as responses to a therapeutic intervention. Biomarkers can be classified as diagnostic, prognostic, predictor, clinical, and therapeutic. In Alzheimer's disease (AD), multiple biomarkers have been reported so far. Nevertheless, finding a specific biomarker in AD remains a major challenge. Three databases, including PubMed, Web of Science, and Scopus were selected with the keywords of Alzheimer's disease, neuroimaging, biomarker, and blood...

Synaptic dysfunction plays a key role in Parkinson's disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. Assessment of plasma EV synaptic proteins for their efficacy as biomarkers in PD and their relationship with disease progression was conducted. In total, 144 participants were enrolled, including 101 people with PD (PwP) and 43 healthy controls (HCs). The changes in plasma EV synaptic protein levels between baseline and 1-year follow-up did not differ significantly in both PwP and HCs...

Apparently, the genomes of many organisms are pervasively transcribed, and long noncoding RNAs (lncRNAs) make up the majority of cellular transcripts. LncRNAs have been reported to play important roles in many biological processes; however, their effects on locomotion are poorly understood. Here, we presented a novel lncRNA, Locomotion Regulatory Gene (LRG), which participates in locomotion by sequestering Synaptotagmin 1 (SYT1). LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body, motoneuron or muscle-expression of LRG...

Members of the phloem protein 16 (PP16) gene family are induced by elicitors in rice and the corresponding proteins from cucurbits, which display RNA binding and intercellular transport activities, are accumulated in phloem sap. These proteins facilitate the movement of protein complexes through the phloem translocation flow and may be involved in the response to water deficit, among other functions. However, there is scant information regarding their function in other plants, including the identification of paralog genes in non-vascular plants and chlorophytes...

Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions...

Fusion pore opening is a transient intermediate state of synaptic vesicle exocytosis, which is highly dynamic and precisely regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex and synaptotagmin-1 (Syt1). Yet, the regulatory mechanism is not fully understood. In this work, using single-channel membrane fusion electrophysiology, we determined that SNAREpins are important for driving fusion pore opening and dilation but incapable of regulating the dynamics. When Syt1 was added, the closing frequency of fusion pores significantly increased, while the radius of fusion pores mildly decreased...

As in most eukaryotic cells, the plant endoplasmic reticulum (ER) network is physically linked to the plasma membrane (PM), forming ER-PM contact sites (EPCS). The protein complex required for maintaining the EPCS is composed of ER integral membrane proteins (e.g., VAP27, synaptotagmins), PM-associated proteins (e.g., NET3C), and the cytoskeleton. Here, we describe methods for studying EPCS structures and identifying possible EPCS-associated proteins. These include using artificially constructed reporters, GFP tagged protein expression followed by image analysis, and immunogold labelling at the ultrastructural level...

SNAP25 is one of three neuronal SNAREs driving synaptic vesicle exocytosis. We studied three mutations in SNAP25 that cause epileptic encephalopathy: V48F, and D166Y in the synaptotagmin-1 (Syt1)-binding interface, and I67N, which destabilizes the SNARE complex. All three mutations reduced Syt1-dependent vesicle docking to SNARE-carrying liposomes and Ca2+ -stimulated membrane fusion in vitro and when expressed in mouse hippocampal neurons. The V48F and D166Y mutants (with potency D166Y > V48F) led to reduced readily releasable pool (RRP) size, due to increased spontaneous (miniature Excitatory Postsynaptic Current, mEPSC) release and decreased priming rates...

Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C-C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME...

Mitochondrial dysfunction and glutamate toxicity are associated with neural disorders, including brain trauma. A review of the literature suggests that toxic and transmission actions of neuronal glutamate are spatially and functionally separated. The transmission pathway utilizes synaptic GluN2A receptors, rapidly released pool of glutamate, evoked release of glutamate mediated by Synaptotagmin 1 and the amount of extracellular glutamate regulated by astrocytes. The toxic pathway utilizes extrasynaptic GluN2B receptors and a cytoplasmic pool of glutamate, which results from the spontaneous release of glutamate mediated by Synaptotagmin 7 and the neuronal 2-oxoglutarate dehydrogenase complex (OGDHC), a tricarboxylic acid (TCA) cycle enzyme...

Dopamine neurons switch from tonic pacemaker activity to high-frequency bursts in response to salient stimuli. These bursts lead to superlinear increases in dopamine release, and the degree of this increase is highly dependent on firing frequency. The superlinearity and frequency-dependence of dopamine release implicates short-term plasticity processes. The presynaptic Ca2+ -sensor synaptotagmin-7 (SYT7) has suitable properties to mediate such short-term plasticity and has been implicated in regulating dopamine release from somatodendritic compartments ...