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Stella-Amrei Kunde, Nils Rademacher, Hanna Zieger, Sarah A Shoichet
Synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors are essential mediators of neurotransmission in the central nervous system. Shisa9/cysteine-knot AMPAR modulating protein 44 (CKAMP44) is a transmembrane protein recently found to be present in AMPA receptor-associated protein complexes. Here, we show that the cytosolic tail of Shisa9/CKAMP44 interacts with multiple scaffold proteins that are important for regulating synaptic plasticity in central neurons. We focussed on the interaction with the scaffold protein PICK1, which facilitates the formation of a tripartite complex with the protein kinase C (PKC) and thereby regulates phosphorylation of Shisa9/CKAMP44 C-terminal residues...
September 2017: FEBS Open Bio
Jan-Øyvind Lorgen, Daniel Lawer Egbenya, Janniche Hammer, Svend Davanger
Overstimulation of glutamate receptors resulting in excessive intracellular calcium concentrations is a major cause of neuronal cell death in epilepsy. The main source of increased calcium concentration during this excitotoxicity is an influx through NMDA subtype of glutamate receptors. The GluR2 hypothesis states that following a neurological insult such as an epileptic seizure, the AMPAR subunit GluR2 protein is down regulated. This increases the likelihood of the formation of GluR2-lacking, calcium-permeable AMPARs which might further enhance the toxicity of the neurotransmitter, glutamate...
August 31, 2017: Epilepsy Research
Ruchi Yadav, Deepshikha Deepshikha, Prachi Srivastava
CHRNA7 is a neurodevelopmental protein involved in differentiation and neurogenesis, which is also named as nicotinic acetylcholine receptors, cholinergic receptor, nicotinic, alpha 7 (neuronal). The protein encoded by this gene forms a homo-oligomeric channel. It is a major component of brain nicotinic receptors displays that are blocked by and sensitive to alpha-bungarotoxin. Studies reports involvement of CHRNA7 protein in different neurological diseases. Non-availability of 3-dimensional (3D) structure leads the study toward structure 3D prediction along with its interaction analysis...
July 2017: Annals of Neurosciences
Maria Fiuza, Christine M Rostosky, Gabrielle T Parkinson, Alexei M Bygrave, Nagaraj Halemani, Marcio Baptista, Ira Milosevic, Jonathan G Hanley
Clathrin-mediated endocytosis (CME) is used to internalize a diverse range of cargo proteins from the cell surface, often in response to specific signals. In neurons, the rapid endocytosis of GluA2-containing AMPA receptors (AMPARs) in response to NMDA receptor (NMDAR) stimulation causes a reduction in synaptic strength and is the central mechanism for long-term depression, which underlies certain forms of learning. The mechanisms that link NMDAR activation to CME of AMPARs remain elusive. PICK1 is a BAR domain protein required for NMDAR-dependent reductions in surface GluA2; however, the molecular mechanisms involved are unclear...
August 30, 2017: Journal of Cell Biology
Yunhong Li, Fan Li, Bin Bai, Zhenyong Wu, Xiaolin Hou, Ying Shen, Yin Wang
It has been previously identified that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are expressed in pancreatic β cells and regulate exocytosis and insulin release. It is known that protein interacting with C‑kinase 1 (PICK1) regulates trafficking and synaptic targeting of AMPARs in the central nervous system. However, it is unknown whether PICK1 regulates glutamate‑induced insulin release in β cells. The present study demonstrated that glutamate‑induced exocytosis was increased in β cells derived from PICK1‑knockout mice...
October 2017: Molecular Medicine Reports
Yuhu Dai, Dong Ren, Qing Yang, Yanmei Cui, Wei Guo, Yingrong Lai, Hong Du, Chuyong Lin, Jun Li, Libing Song, Xinsheng Peng
Backgroud:Constitutive activation of TGF-β signalling is a well-recognised mechanism in bone metastasis of prostate cancer (PCa). Protein Interacting with PRKCA 1 (PICK1) is a critical negative regulator of the TGF-β pathway. However, the clinical significance and biological role of PICK1 in PCa bone metastasis remain obscure. METHODS: PICK1 expression is evaluated by immunohistochemistry (IHC) in 198 PCa patients. Statistical analysis is performed to explore correlation between PICK1 expression and clinicopathological features in PCa patients...
August 22, 2017: British Journal of Cancer
Yi-Ting Chen, Chieh-Hsin Lin, Chiung-Hsien Huang, Wen-Miin Liang, Hsien-Yuan Lane
The gene of protein interacting with C kinase 1 alpha (PICK1) has been implicated in schizophrenia, nevertheless, conflicting results existed. However, its role in cognitive function remains unclear. Besides, cognitive deficits impair the long-term outcome. We explored whether the polymorphisms of PICK1 (rs2076369, rs3952) affected cognitive functions in schizophrenic patients. We analyzed 302 patients and tested the differences of cognitive functions, clinical symptoms between genetic groups. We also used general linear model to analyze the effect of PICK1 genetic polymorphisms on cognitive functions...
May 15, 2017: Scientific Reports
Dipen Rajgor, Maria Fiuza, Gabrielle T Parkinson, Jonathan G Hanley
MicroRNAs (miRNAs) are important regulators of localized mRNA translation in neuronal dendrites. The presence of RNA-induced silencing complex proteins in these compartments and the dynamic miRNA expression changes that occur in response to neuronal stimulation highlight their importance in synaptic plasticity. Previously, we demonstrated a novel interaction between the major RNA-induced silencing complex component Argounaute-2 (Ago2) and the BAR (bin/amphiphysin/rvs) domain protein PICK1. PICK1 recruits Ago2 to recycling endosomes in dendrites, where it inhibits miRNA-mediated translational repression...
June 9, 2017: Journal of Biological Chemistry
Youssef Aissouni, Abderrahim El Guerrab, Al Mahdy Hamieh, Jérémy Ferrier, Maryse Chalus, Diane Lemaire, Stéphanie Grégoire, Monique Etienne, Alain Eschalier, Denis Ardid, Eric Lingueglia, Fabien Marchand
Chronic pain is associated with anxiety and depression episodes. The amygdala plays a key role in the relationship between emotional responses and chronic pain. Here, we investigated the role of Acid-Sensing Ion Channels 1a within the basolateral amygdala (BLA), in pain and associated anxiety in a rat model of monoarthritis (MoAr). Administration within the BLA of PcTx1 or mambalgin-1, two specific inhibitors of ASIC1a-containing channels significantly inhibited pain and anxiety-related behaviours in MoAr rats...
March 2, 2017: Scientific Reports
Jun Nomura, Geetha Kannan, Toru Takumi
Elucidating the molecular basis of complex human psychiatric disorders is challenging due to the multitude of factors that underpin these disorders. Genetic and chromosomal changes are two factors that have been suggested to be involved in psychiatric disorders. Indeed, numerous risk loci have been identified in autism spectrum disorders, schizophrenia, and related psychiatric disorders. Here, we introduce genetic animal models that disturb excitatory-inhibitory balance in the brain and animal models mirroring human chromosomal abnormalities, both of which may be implicated in autism spectrum disorder pathophysiology...
March 20, 2017: Psychiatry and Clinical Neurosciences
C Haglerød, S Hussain, Y Nakamura, J Xia, F-M S Haug, O P Ottersen, J M Henley, S Davanger
Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus...
March 6, 2017: Neuroscience
Chao Liu, Zhenhua Song, Lina Wang, Haiyan Yu, Weixiao Liu, Yongliang Shang, Zhiliang Xu, Haichao Zhao, Fengyi Gao, Jiamin Wen, Linan Zhao, Yaoting Gui, Jianwei Jiao, Fei Gao, Wei Li
Sirt1 is a member of the sirtuin family of proteins and has important roles in numerous biological processes. Sirt1(-/-) mice display an increased frequency of abnormal spermatozoa, but the mechanism of Sirt1 in spermiogenesis remains largely unknown. Here, we report that Sirt1 might be directly involved in spermiogenesis in germ cells but not in steroidogenic cells. Germ cell-specific Sirt1 knockout mice were almost completely infertile; the early mitotic and meiotic progression of germ cells in spermatogenesis were not obviously affected after Sirt1 depletion, but subsequent spermiogenesis was disrupted by a defect in acrosome biogenesis, which resulted in a phenotype similar to that observed in human globozoospermia...
February 1, 2017: Development
Gitte B Christiansen, Katrine H Andersen, Sarah Riis, Anders Nykjaer, Ulrik Bolcho, Morten S Jensen, Mai Marie Holm
Correct function of glutamate receptors in the postsynaptic density is crucial to synaptic function and plasticity. SorCS3 (sortilin-related receptor CNS expressed 3) is a sorting receptor which previously has been shown to interact with the key postsynaptic proteins; PSD-95 and PICK1. In this study, we employed electrophysiological analyses of acute brain slices combined with immunohistochemistry to define the role of SorCS3 in hippocampal synapses in CA1 and the dentate gyrus. We analyzed a juvenile (P17-21) and a young adult (P55-65) group of animals from a Sorcs3 knockout mouse model...
March 2017: Hippocampus
Feng Cao, Zikai Zhou, Xingxiu Pan, Celeste Leung, Wei Xie, Graham Collingridge, Zhengping Jia
Long lasting synaptic plasticity involves both functional and morphological changes, but how these processes are molecularly linked to achieve coordinated plasticity remains poorly understood. Cofilin is a common target of multiple signaling pathways at the synapse and is required for both functional and spine plasticity, but how it is regulated is unclear. In this study, we investigate whether the involvement of cofilin in plasticity is developmentally regulated by examining the role of cofilin in hippocampal long-term depression (LTD) in both young (2 weeks) and mature (2 months) mice...
January 2017: Neuropharmacology
Zhifen Wang, Yuan Yuan, Keliang Xie, Xiaohong Tang, Linlin Zhang, Jiying Ao, Nan Li, Yu Zhang, Suqian Guo, Guolin Wang
BACKGROUND: Remifentanil is used widely in clinical anesthesia because it induces more rapid and more common hyperalgesia than other opioid analgesics. Activation of N-methyl-D-aspartate (NMDA) receptors takes a pivotal part in remifentanil-induced hyperalgesia. Like NMDA receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are excitatory ion glutamate receptors in postsynaptic membrane, which are involved in the transmission of both acute and chronic pain...
September 2016: Anesthesia and Analgesia
Jocelyn Widagdo, Huaqiang Fang, Se Eun Jang, Victor Anggono
Dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses plays an important role in synaptic plasticity. We previously reported that the protein kinase C and casein kinase II substrate in neurons (PACSIN) forms a complex with AMPARs through its interaction with the protein interacting with C-kinase 1 (PICK1) to regulate NMDA receptor (NMDAR)-induced AMPAR endocytosis and cerebellar long-term depression. However, the molecular mechanism by which PACSIN regulates the dynamics of AMPAR trafficking remains unclear...
2016: Scientific Reports
Bingling Dai, Wenjie Wang, Yujiao Ma, Rui Liu, Yanmin Zhang
Colorectal cancer is a common gastrointestinal malignancy worldwide and it is a lethal and aggressive malignancy with a dismal prognosis. In the present study, we investigated the effect of taspine derivative 12k on human colorectal cancer targeted at EphrinB2 and its PDZ. The results indicated that 12k could bind to EphrinB2 and showed a higher suppressive effect on EphrinB2/HEK293 than on HEK293 cells. Caco‑2 cells were screened for high expression of EphrinB2. We found that 12k not only significantly decreased Caco‑2 cell viability and colony formation but impaired migration...
September 2016: Oncology Reports
Parastoo Modarres, Somayeh Tanhaei, Marziyeh Tavalaee, Kamran Ghaedi, Mohammad Reza Deemeh, Mohammad Hossein Nasr-Esfahani
BACKGROUND: Globozoospermia is a rare syndrome with an incidence of less than 0.1% among infertile men. Researchers have recently identified a large deletion, about 200 kbp, encompassing the whole length of DPY19L2 or mutations in SPATA16 and PICK1 genes associated with globozoospermia. The aim of this study was to analyze the DPY19L2 gene deletion using polymerase chain reaction technique for the exons 1, 48, 11 and 22 as well as break point (BP) "a" in globozoospermic men. MATERIALS AND METHODS: In this experimental study, genome samples were collected from 27 men with globozoospermia (cases) and 36 fertile individuals (controls), and genomic analysis was carried out on each sample...
July 2016: International Journal of Fertility & Sterility
Qing-Ping Tang, Qin Shen, Li-Xiang Wu, Xiang-Ling Feng, Hui Liu, Bei Wu, Xiao-Song Huang, Gai-Qing Wang, Zhong-Hao Li, Zun-Jing Liu
Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training...
July 2016: Journal of Zhejiang University. Science. B
Laura V Gonzalez Bosc, Danielle R Plomaritas, Lindsay M Herbert, Wieslawa Giermakowska, Carly Browning, Nikki L Jernigan
The development of chronic hypoxia (CH)-induced pulmonary hypertension is associated with increased pulmonary arterial smooth muscle cell (PASMC) Ca(2+) influx through acid-sensing ion channel-1 (ASIC1) and activation of the Ca(2+)/calcineurin-dependent transcription factor known as nuclear factor of activated T-cells isoform c3 (NFATc3). Whether Ca(2+) influx through ASIC1 contributes to NFATc3 activation in the pulmonary vasculature is unknown. Furthermore, both ASIC1 and calcineurin have been shown to interact with the scaffolding protein known as protein interacting with C kinase-1 (PICK1)...
July 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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