| 1 | Gene 2005 Mar 348: 123-34 |
|---|---|
| PMID | 15777718 |
| Title | Effects of methylation of non-CpG sequence in the promoter region on the expression of human synaptotagmin XI (syt11). |
| Abstract | We have studied the effects of methylation of the promoter region on the expression of human synaptotagmin XI (SYT11), a gene implicated in the onset ofschizophrenia. Sequence analysis showed that cytosine residues not in the CpG sequence, but still within the promoter region of the gene, are partially methylated. The methylated cytosine residues are located in the mRNA-coding (minus) strand of the promoter region (mCmCTTmCTTmCmC). Gel mobility shift assays showed that when the cytosine residues are methylated, the binding activity of an Sp family protein, a transcription factor, to the region is significantly reduced. Furthermore, transient transcription assays using artificially methylated promoter sequences showed that methylation did reduce the expression of the reporter gene. The biological significance of the finding is discussed in respect to the effect of methylation of non-CpG sequences in promoter regions on gene expression. |
| SCZ Keywords | schizophrenia |
| 2 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007 Apr 144B: 332-40 |
| PMID | 17192956 |
| Title | Synaptotagmin XI as a candidate gene for susceptibility to schizophrenia. |
| Abstract | Synaptotagmin XI (SYT11) is a member of the synaptotagmin family, which is localized in cells either in synaptic vesicles or the cellular membrane, and is known to act as a calcium sensor. TheSYT11gene is located on chromosome locus 1q21-q22, which was previously reported as a major susceptibility locus of familialschizophrenia. Here, we present evidence for an association between the number of 33-bp repeats in the promoter region of theSYT11gene andschizophrenia. We found that the transcriptional activity of the gene is affected by the number of 33-bp repeats, which include an Sp1 binding site, suggesting that the excessive expression ofSYT11can be associated withschizophrenia. Another (single nucleotide) polymorphism in theSYT115'UTR region, where the potent transcription factor YY1 can bind, also affects the transcriptional activity ofSYT11. |
| SCZ Keywords | schizophrenia |
| 3 | Neuroscience 2012 Dec 225: 35-43 |
| PMID | 22960622 |
| Title | Developmental expression and subcellular distribution of synaptotagmin 11 in rat hippocampus. |
| Abstract | Synaptotagmins are required for Ca(2+)-dependent membrane-trafficking in either neuronal synaptic vesicles or cellular membranes. Previous reports suggested that the synaptotagmin 11 (SYT11) gene is involved in the development ofschizophreniabased on the genomic analysis of patients. Parkin protein binds to the C2 domains ofSYT11which leads to the polyubiquitination ofSYT11. However, where and howSYT11performs its role in the brain is largely unknown. Here, we report thatSYT11is expressed mainly in the brain. In addition, exogenously expressedSYT11in HEK293 cells can form higher molecular weight complex via its transmembrane domain. Also,SYT11is targeted to both dendrite and axon compartments. Immunocytochemistry showed thatSYT11is juxtaposed to postsynaptic markers in both excitatory and inhibitory synapses. Both neuroligin 1 and 2, which are postsynaptic cell adhesion molecules and differentially induce excitatory and inhibitory presynapses, respectively, recruitSYT11在神经元coculture。Immunogold电子microscopy analysis revealed thatSYT11exists mainly in presynaptic neurotransmitter vesicles and plasma membrane, and rarely in postsynaptic sites. These results suggest thatSYT11may contribute to the regulation of neurotransmitter release in the excitatory and inhibitory presynapses, and postsynapse-targeted membrane trafficking in dendrites. |
| SCZ Keywords | schizophrenia |
| 4 | EMBO Rep. 2016 Jan 17: 47-63 |
| PMID | 26589353 |
| Title | Synaptotagmin-11 inhibits clathrin-mediated and bulk endocytosis. |
| Abstract | 精确、高效的内吞作用是至关重要的vesicle recycling during a sustained neurotransmission. The regulation of endocytosis has been extensively studied, but inhibitors have rarely been found. Here, we show that synaptotagmin-11 (SYT11), a non-Ca(2+)-binding Syt implicated inschizophreniaand Parkinson's disease, inhibits clathrin-mediated endocytosis (CME) and bulk endocytosis in dorsal root ganglion neurons. The frequency of both types of endocytic event increases inSYT11knockdown neurons, while the sizes of endocytosed vesicles and the kinetics of individual bulk endocytotic events remain unaffected. Specifically, clathrin-coated pits and bulk endocytosis-like structures increase on the plasma membrane inSYT11-knockdown neurons. Structural-functional analysis reveals distinct domain requirements forSYT11function in CME and bulk endocytosis. Importantly,SYT11also inhibits endocytosis in hippocampal neurons, implying a general role ofSYT11in neurons. Taken together, we propose thatSYT11functions to ensure precision in vesicle retrieval, mainly by limiting the sites of membrane invagination at the early stage of endocytosis. |
| SCZ Keywords | schizophrenia |