| 1 | Gene 2005 Mar 348: 123-34 |
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| 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 of schizophrenia. 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 |
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| 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. The SYT11 gene is located on chromosome locus 1q21-q22, which was previously reported as a major susceptibility locus of familial schizophrenia. Here, we present evidence for an association between the number of 33-bp repeats in the promoter region of the SYT11 gene and schizophrenia. 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 of SYT11 can be associated with schizophrenia. Another (single nucleotide) polymorphism in the SYT11 5'UTR region, where the potent transcription factor YY1 can bind, also affects the transcriptional activity of SYT11. |
| SCZ Keywords | schizophrenia |
| 3 | Neuroscience 2012 Dec 225: 35-43 |
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| 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 of schizophrenia based on the genomic analysis of patients. Parkin protein binds to the C2 domains of SYT11 which leads to the polyubiquitination of SYT11. However, where and how SYT11 performs its role in the brain is largely unknown. Here, we report that SYT11 is expressed mainly in the brain. In addition, exogenously expressed SYT11 in HEK293 cells can form higher molecular weight complex via its transmembrane domain. Also, SYT11 is targeted to both dendrite and axon compartments. Immunocytochemistry showed that SYT11 is 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, recruit SYT11 in neuron coculture. Immunogold electron microscopy analysis revealed that SYT11 exists mainly in presynaptic neurotransmitter vesicles and plasma membrane, and rarely in postsynaptic sites. These results suggest that SYT11 may 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 |
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| PMID | 26589353 |
| Title | Synaptotagmin-11 inhibits clathrin-mediated and bulk endocytosis. |
| Abstract | Precise and efficient endocytosis is essential for 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 in schizophrenia and 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 in SYT11 knockdown 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 in SYT11-knockdown neurons. Structural-functional analysis reveals distinct domain requirements for SYT11 function in CME and bulk endocytosis. Importantly, SYT11 also inhibits endocytosis in hippocampal neurons, implying a general role of SYT11 in neurons. Taken together, we propose that SYT11 functions to ensure precision in vesicle retrieval, mainly by limiting the sites of membrane invagination at the early stage of endocytosis. |
| SCZ Keywords | schizophrenia |