Regulation of Dendritic Spines, Spatial Memory, and Embryonic Development by the TANC Family of PSD-95-Interacting Proteins

Han, Seungnam; Nam, Jungyong; Li, Yan; Kim, Se‐Ho; Cho, Suk Hee; Cho, Yi Sul; Choi, So Yeon; Choi, June-Seok; Han, Ki-Hoon; Kim, Youngrim; Na, Moonseok; Kim, Hyun; Bae, Yong Chul; Choi, Se Young; Kim, Eunjoon

doi:10.1523/jneurosci.3128-10.2010

Cited by 63 publications

(82 citation statements)

References 39 publications

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“…Interestingly, Mbnl2 knockout mice exhibit impaired learning on a hippocampal-dependent task, a decrease in NMDAR-mediated synaptic transmission, and an impairment of hippocampal synaptic plasticity. Several of the mis-regulated splicing events identified during this study might contribute to these impairments, including Cacna1d (McKinney et al, 2009), Tanc2 (Han et al, 2010), Ndrg4 (Yamamoto et al, 2011) and Grin1 (Shimizu et al, 2000). For example, DM1 patients exhibit increased expression of a splice variant of GRIN1 that includes exon 5 (Jiang et al, 2004), which is thought to contribute to the age-related decline in frontotemporal functions, including memory (Modoni et al, 2008; Romeo et al, 2010; Weber et al, 2010).…”

Section: Discussionmentioning

confidence: 84%

Muscleblind-like 2-Mediated Alternative Splicing in the Developing Brain and Dysregulation in Myotonic Dystrophy

Charizanis

Lee

Batra

et al. 2012

Neuron

302

466

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SUMMARY The RNA-mediated disease model for myotonic dystrophy (DM) proposes that microsatellite C(C)TG expansions express toxic RNAs which disrupt splicing regulation by altering MBNL1 and CELF1 activities. While this model explains DM manifestations in muscle, less is known about the effects of C(C)UG expression on the brain. Here, we report that Mbnl2 knockout mice develop several DM-associated CNS features including abnormal REM sleep propensity and deficits in spatial memory. Mbnl2 is prominently expressed in the hippocampus and Mbnl2 knockouts show a decrease in NMDAR synaptic transmission and impaired hippocampal synaptic plasticity. While Mbnl2 loss did not significantly alter target transcript levels in the hippocampus, mis-regulated splicing of hundreds of exons was detected using splicing microarrays, RNA-seq and HITS-CLIP. Importantly, the majority of the Mbnl2-regulated exons examined were similarly mis-regulated in DM. We propose that major pathological features of the DM brain result from disruption of the MBNL2-mediated developmental splicing program.

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Section: Discussionmentioning

confidence: 84%

Muscleblind-like 2-Mediated Alternative Splicing in the Developing Brain and Dysregulation in Myotonic Dystrophy

Charizanis

Lee

Batra

et al. 2012

Neuron

302

466

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“…Calpain-5 is a non-classical member of the calpain family that is highly expressed in the CNS [49], but whether it functions the same way as the other members in synaptic activity and neurotoxixity is unknown. Some proteins are associated with neurite extension/synapse maturation or neuronal viability during neural development (Abl interactor [50,51], gamma-adducin [52,53], FKBP8 [54,55], hippocalcin [56,57], CD47 [58], Nova-1 [59,60], TANC2 [61] and Teneurin [62,63]). And several listed proteins have been reported to participate in cell death mechanisms in adult brain ischemia (Dynamin-1 [64,65], FKBP8 [66], CD47 [67,68] and TDP-43 [69,70]).…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis of Mouse Cortex Postsynaptic Density following Neonatal Brain Hypoxia-Ischemia

Shao

Wang²,

Guan³

et al. 2017

Dev Neurosci

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Proteomics of the synapses and postsynaptic densities (PSDs) have provided a deep understanding of protein composition and signal networks in the adult brain, which underlie neuronal plasticity and neurodegenerative or psychiatric disorders. However, there is a paucity of knowledge about the architecture and organization of PSDs in the immature brain, and how it is modified by brain injury in an early developing stage. Mass spectrometry (MS)-based proteomic analysis was performed on PSDs prepared from cortices of postnatal day 9 naïve mice or pups which had suffered hypoxic-ischemic (HI) brain injury. 512 proteins of different functional groups were identified from PSDs collected 1 h after HI injury, among which 60 have not been reported previously. Seven newly identified proteins involved in neural development were highlighted. HI injury increased the yield of PSDs at early time points upon reperfusion, and multiple proteins were recruited into PSDs following the insult. Quantitative analysis was performed using spectral counting, and proteins whose relative expression was more than 50% up- or downregulated compared to the sham animals 1 h after HI insult were reported. Validation with Western blotting demonstrated changes in expression and phosphorylation of the N-methyl-D-aspartate receptor, activation of a series of postsynaptic protein kinases and dysregulation of scaffold and adaptor proteins in response to neonatal HI insult. This work, along with other recent studies of synaptic protein profiling in the immature brain, builds a foundation for future investigation on the molecular mechanisms underlying developing plasticity. Furthermore, it provides insights into the biochemical changes of PSDs following early brain hypoxia-ischemia, which is helpful for understanding not only the injury mechanisms, but also the process of repair or replenishment of neuronal circuits during recovery from brain damage.

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“…S6), allowing for the speculation that lncRNA AB074278 may regulate (by enhancing) the expression of TANC2 in cis (35). Little is known about the function of TANC2, although it is believed to play a role in embryonic development (46). Although these data are promising, we were keen to select mRNAs whose expression was abnormal in urothelial cancer and correlated to AB074278.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Long Noncoding RNAs in Bladder Cancer

Schmitz

Borkowska

Drayton

et al. 2014

Clinical Cancer Research

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Purpose: Loss of epigenetic gene regulation through altered long noncoding RNA (lncRNA) expression seems important in human cancer. LncRNAs have diagnostic and therapeutic potential, and offer insights into the biology disease, but little is known of their expression in urothelial cancer. Here, we identify differentially expressed lncRNAs with potential regulatory functions in urothelial cancer.Experimental Design: The expression of 17,112 lncRNAs and 22,074 mRNAs was determined using microarrays in 83 normal and malignant urothelial (discovery) samples and selected RNAs with qPCR in 138 samples for validation. Significantly differentially expressed RNAs were identified and stratified according to tumor phenotype. siRNA knockdown, functional assays, and whole-genome transcriptomic profiling were used to identify potential roles of selected lncRNAs.Results: We observed upregulation of many lncRNAs in urothelial cancer that was distinct to corresponding, more balanced changes for mRNAs. In general, lncRNA expression reflected disease phenotype. We identified 32 lncRNAs with potential roles in disease progression. Focusing upon a promising candidate, we implicate upregulation of AB074278 in apoptosis avoidance and the maintenance of a proproliferative state in cancer through a potential interaction with EMP1, a tumor suppressor and a negative regulator of cell proliferation.Conclusions: We report differential expression profiles for numerous lncRNA in urothelial cancer. We identify phenotype-specific expression and a potential mechanistic target to explain this observation.

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Regulation of Dendritic Spines, Spatial Memory, and Embryonic Development by the TANC Family of PSD-95-Interacting Proteins

Cited by 63 publications

References 39 publications

Muscleblind-like 2-Mediated Alternative Splicing in the Developing Brain and Dysregulation in Myotonic Dystrophy

Muscleblind-like 2-Mediated Alternative Splicing in the Developing Brain and Dysregulation in Myotonic Dystrophy

Proteomic Analysis of Mouse Cortex Postsynaptic Density following Neonatal Brain Hypoxia-Ischemia

Identification of Differentially Expressed Long Noncoding RNAs in Bladder Cancer

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