Developmental expression and subcellular distribution of synaptotagmin 11 in rat hippocampus

Yeo, Hye Min; Kim, H.-w.; Mo, Jiwon; Lee, D.; Han, Seung Baek; Hong, Seung No; Koh, Min Jung; Sun, Woong; Choi, Se Young; Rhyu, Im Joo; Kim, H.; Lee, H.W.

doi:10.1016/j.neuroscience.2012.08.062

Cited by 9 publications

(9 citation statements)

References 49 publications

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“…These organelles are broadly distributed in neuronal somas and dendritic processes, traffic in axonal and dendritic shafts in a bidirectional manner, and, evidently, do not undergo synchronized exocytosis during synaptic excitation. Our results are at odds with a prior report suggesting that Syt11 is enriched at synapses and localized to synaptic plasma membranes and SVs (Yeo et al 2012). This discrepancy may be attributable to the limited specificity of the commercial antibody used by Yeo et al (2012), since our conclusions are supported by analyses of native and recombinant proteins with multiple validated readouts.…”

Section: Discussioncontrasting

confidence: 99%

“…Our results are at odds with a prior report suggesting that Syt11 is enriched at synapses and localized to synaptic plasma membranes and SVs (Yeo et al 2012). This discrepancy may be attributable to the limited specificity of the commercial antibody used by Yeo et al (2012), since our conclusions are supported by analyses of native and recombinant proteins with multiple validated readouts. Although the properties of Syt11 vesicles are reminiscent of vesicles that recruit Syt4 (Dean et al 2012), the consequences of genetic ablation of these two Syt isoforms on neural circuit function are different, as discussed below.…”

Section: Discussioncontrasting

confidence: 99%

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Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity

et al. 2019

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Synaptotagmin-11 (Syt11) is a Synaptotagmin isoform that lacks an apparent ability to bind calcium, phospholipids, or SNARE proteins. While human genetic studies have linked mutations in the Syt11 gene to schizophrenia and Parkinson's disease, the localization or physiological role of Syt11 remain unclear. We found that in neurons, Syt11 resides on abundant vesicles that differ from synaptic vesicles and resemble trafficking endosomes. These vesicles recycle via the plasma membrane in an activity-dependent manner, but their exocytosis is slow and desynchronized. Constitutive knockout mice lacking Syt11 died shortly after birth, suggesting Syt11-mediated membrane transport is required for survival. In contrast, selective ablation of Syt11 in excitatory forebrain neurons using a conditional knockout did not affect life span but impaired synaptic plasticity and memory. Syt11-deficient neurons displayed normal secretion of fast neurotransmitters and peptides but exhibited a reduction of long-term synaptic potentiation. Hence, Syt11 is an essential component of a neuronal vesicular trafficking pathway that differs from the wellcharacterized synaptic vesicle trafficking pathway but is also essential for life.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity

et al. 2019

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“…Syt XI is the most abundant Syt isoform in astrocytes and is expressed more abundantly in the astrocytes as compared with the neurons; 27,28,30 however, its subcellular localization in astrocytes is not known. 41,42 Use of western blot analysis confirmed expression of Syt XI protein in primary astrocytes (Figure 4c). Using cell fractionation we found that endogenous Syt XI is enriched in the lysosome fractions (Figure 4d), demonstrating its localization on astrocyte lysosomes.…”

Section: Syt XI Regulates Lysosomal Exocytosis In Astrocytesmentioning

confidence: 75%

Injured astrocytes are repaired by Synaptotagmin XI-regulated lysosome exocytosis

et al. 2015

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Astrocytes are known to facilitate repair following brain injury; however, little is known about how injured astrocytes repair themselves. Repair of cell membrane injury requires Ca 2+ -triggered vesicle exocytosis. In astrocytes, lysosomes are the main Ca 2+ -regulated exocytic vesicles. Here we show that astrocyte cell membrane injury results in a large and rapid calcium increase. This triggers robust lysosome exocytosis where the fusing lysosomes release all luminal contents and merge fully with the plasma membrane. In contrast to this, receptor stimulation produces a small sustained calcium increase, which is associated with partial release of the lysosomal luminal content, and the lysosome membrane does not merge into the plasma membrane. In most cells, lysosomes express the synaptotagmin (Syt) isoform Syt VII; however, this isoform is not present on astrocyte lysosomes and exogenous expression of Syt VII on lysosome inhibits their exocytosis. Deletion of one of the most abundant Syt isoform in astrocyte -Syt XI -suppresses astrocyte lysosome exocytosis. This identifies lysosome as Syt XI-regulated exocytic vesicle in astrocytes. Further, inhibition of lysosome exocytosis (by Syt XI depletion or Syt VII expression) prevents repair of injured astrocytes. These results identify the lysosomes and Syt XI as the sub-cellular and molecular regulators, respectively of astrocyte cell membrane repair.

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“…Rat hippocampus studies suggest that it contributes to the regulation of neurotransmitter release in the excitatory and inhibitory presynapses, and to postsynapse-targeted membrane trafficking in dendrites. (112)(113)(114)(115)(116)(117)(118) VAMP4 and STX6 These are components of a protein complex involved in vesicle-membrane fusion and important for cell adhesion. STX6 has been implicated in a GWAS of the tauopathy progressive supranuclear palsy.…”

Section: Syt11mentioning

confidence: 99%

Transcriptome study of differential expression in schizophrenia

Sanders

Göring

Duan

et al. 2013

Human Molecular Genetics

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Schizophrenia genome-wide association studies (GWAS) have identified common SNPs, rare copy number variants (CNVs) and a large polygenic contribution to illness risk, but biological mechanisms remain unclear. Bioinformatic analyses of significantly associated genetic variants point to a large role for regulatory variants. To identify gene expression abnormalities in schizophrenia, we generated whole-genome gene expression profiles using microarrays on lymphoblastoid cell lines (LCLs) from 413 cases and 446 controls. Regression analysis identified 95 transcripts differentially expressed by affection status at a genome-wide false discovery rate (FDR) of 0.05, while simultaneously controlling for confounding effects. These transcripts represented 89 genes with functions such as neurotransmission, gene regulation, cell cycle progression, differentiation, apoptosis, microRNA (miRNA) processing and immunity. This functional diversity is consistent with schizophrenia's likely significant pathophysiological heterogeneity. The overall enrichment of immune-related genes among those differentially expressed by affection status is consistent with hypothesized immune contributions to schizophrenia risk. The observed differential expression of extended major histocompatibility complex (xMHC) region histones (HIST1H2BD, HIST1H2BC, HIST1H2BH, HIST1H2BG and HIST1H4K) converges with the genetic evidence from GWAS, which find the xMHC to be the most significant susceptibility locus. Among the differentially expressed immune-related genes, B3GNT2 is implicated in autoimmune disorders previously tied to schizophrenia risk (rheumatoid arthritis and Graves' disease), and DICER1 is pivotal in miRNA processing potentially linking to miRNA alterations in schizophrenia (e.g. MIR137, the second strongest GWAS finding). Our analysis provides novel candidate genes for further study to assess their potential contribution to schizophrenia.

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Developmental expression and subcellular distribution of synaptotagmin 11 in rat hippocampus

Cited by 9 publications

References 49 publications

Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity

Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity

Injured astrocytes are repaired by Synaptotagmin XI-regulated lysosome exocytosis

Transcriptome study of differential expression in schizophrenia

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