Ask about this productRelated genes to: SYT2 Blocking Peptide
- Gene:
- SYT2 NIH gene
- Name:
- synaptotagmin 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1q32.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-09-27
- Date modifiied:
- 2015-11-20
Related products to: SYT2 Blocking Peptide
Related articles to: SYT2 Blocking Peptide
- Neurotransmitter co-transmission contributes to diverse physiological processes throughout the mammalian brain, including sensory integration, motivational control, and social behaviors. Projections from the globus pallidus internus (GPi; the entopeduncular nucleus, EPN, in rodents) to the lateral habenula (LHb) are well-characterized by the co-transmission of both GABA and glutamate. These dual-release inputs modulate behavioral states in chronically learned helpless (cLH) rats, influencing both the onset and recovery of pathological phenotypes. Here, we employed confocal 3D reconstructions that confirmed the presence of both vesicular transporters VGAT and VGLUT2 in EPN axon terminals within the LHb. Further investigation revealed that GABA and glutamate are packaged in distinct vesicle populations within individual presynaptic terminals. Notably, the calcium (Ca) sensors Synaptotagmin-2 (Syt2) and Synaptotagmin-3 (Syt3) are highly expressed in the EPN whereas expression of the canonical Ca sensor, Synaptotagmin 1 (Syt1), is downregulated. Additionally, using confocal microscopy, we observed selective spatial correlations of Syt2 and VGLUT2 and between Syt3 and VGAT in LHb axon terminals. These observations strongly suggested that Syt2 serves as the predominant Ca sensor for glutamatergic vesicle fusion, and Syt3 serves as the predominant Ca sensor for GABAergic vesicle fusion in the LHb. To test this hypothesis, we employed targeted antisense oligonucleotide (ASO) knockdown of Syt2 and Syt3 in EPN neurons and measured LHb glutamatergic and GABAergic currents. Syt2 knockdown resulted in an increase in mEPSC frequency, amplitude, half-width and decay, suggesting increased glutamate vesicle release probability and increased glutamate vesicle packing. However, Syt2 knockdown had no influence on mIPSCs amplitude or frequency. On the other hand, Syt3 knockdown had no apparent effect on glutamate release but caused an increase in mIPSC frequency suggesting increased quantal release probability of GABA. Together, these findings identify a molecular mechanism by which synaptotagmin isoforms govern differential glutamate and GABA release at EPN dual-transmitter terminals in the LHb. These results provide evidence for presynaptic mechanisms regulating excitatory-inhibitory balance within this brain structure and importantly provide molecular targets for pharmacological intervention. - Source: PubMed
Publication date: 2026/04/04
White Dustin NKushner J KeenanWinther Kelly EMcGovern Dillon JBasta TamaraDonaldson Zoe RHoeffer Charles ARoot David HStowell Michael H B - Members of the Synaptotagmin (SYT) family of synaptic vesicle (SV) proteins contain two Ca binding C2 domains (C2A and C2B) that regulate the timing and probability of SV fusion. Recently, dominant mutations in SYT1, present at most CNS synapses, and SYT2, abundant in the PNS, have been found to cause human neurological diseases. Most pathogenic alleles localize to the C2B Ca binding pocket, although mutations outside of this region have been identified. Here we report the effects of a large array of disease-associated human SYT point mutations on synaptic transmission using the model to define their mechanism of action. Mutations in the C2B Ca binding pocket were the most severe and acted in a dominant-negative manner to decrease evoked release. Indeed, mutations in the C2B Ca binding pocket were a privileged site for dominant-negative effects on SV fusion. Molecular dynamics simulations indicate these mutations alter the topology of the C2B Ca binding pocket and disrupt Ca-triggered membrane insertion. Several mutations outside of this region acted through a gain-of-function mechanism to enhance neurotransmitter release, while others caused the protein to undergo degradation. Consistent with this latter subset acting via haploinsufficiency, heterozygotes lacking one copy of SYT1 displayed a ~40% decrease in evoked release. These data indicate C2B Ca binding pocket mutations act dominantly to poison the fusion machinery and block release sites, while mutations outside of this region cause haploinsufficiency or gain-of-function effects with milder effects on synaptic output and behavioral phenotypes. - Source: PubMed
Publication date: 2026/03/18
Guan ZhuoBykhovskaia MariaLittleton J Troy - Synaptotagmin-2-related disease is an ultrarare entity, characterized by distal muscle atrophy in the lower limbs, foot deformities and, in some cases, neonatal hypotonia. Most mutations are concentrated in the C2B domain, critical for the protein's function. Here, our objective is to review clinical, electrophisiological and pathological aspects of this disease. - Source: PubMed
Fontana Pedro NogueiraCorreia Carolina da CunhaFerreira da Silva Ana Marina DutraCarvalho Alzira Alves de Siqueira - To investigate the value of the radiomics features extracted from the contrast-free synthetic MRI (SyMRI) and apparent diffusion coefficient (ADC) in the early prediction of treatment response to neoadjuvant chemotherapy (NAC) in breast cancer. - Source: PubMed
Publication date: 2025/08/05
Zhang YanniZhao RuimengDu SiyaoGao SiXie LizhiKang ZhongqiYu JiapingChen BoZhang Lina - In learning and memory, the encoding of experience is converted into memory ensembles, affecting future behavior. The mechanisms underlying such memory formation are poorly understood, but parvalbumin-expressing (PV) interneurons might be important due to their roles in shaping offline network activity. Here, we addressed the roles of early- and late-born PV neuron subpopulations in memory formation and consolidation in mice. Subpopulation-specific silencing of early-born Syt2+ hippocampal PV neurons during an early 15-min time window upon learning prevented allocation of cFos expression to the correct learning-related principal neuron (PN) subpopulation and memory formation. Conversely, late-born Syt2- PV neurons were specifically required for subsequent memory consolidation and recall, but not PN allocation. During memory formation, the recruitment of one PN subpopulation prevented the subsequent recruitment of the alternative subpopulation. Therefore, memory ensemble allocation to the correct PN subpopulation is a critical early step in memory formation, specifically depending on the activity of Syt2+ early-born PV neurons. - Source: PubMed
Publication date: 2025/08/12
Valbuena SergioBhandari KomalUdhayachandran AnnapooraniTripodi MatteoCaroni Pico