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https://www.readbyqxmd.com/read/29768204/an-amphipathic-helix-directs-cellular-membrane-curvature-sensing-and-function-of-the-bar-domain-protein-pick1
#1
Rasmus Herlo, Viktor K Lund, Matthew D Lycas, Anna M Jansen, George Khelashvili, Rita C Andersen, Vikram Bhatia, Thomas S Pedersen, Pedro B C Albornoz, Niklaus Johner, Ina Ammendrup-Johnsen, Nikolaj R Christensen, Simon Erlendsson, Mikkel Stoklund, Jannik B Larsen, Harel Weinstein, Ole Kjærulff, Dimitrios Stamou, Ulrik Gether, Kenneth L Madsen
BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29753867/topiramate-mitigates-3-nitropropionic-acid-induced-striatal-neurotoxicity-via-modulation-of-ampa-receptors
#2
Heba N Shalaby, Dalia M El-Tanbouly, Hala F Zaki
Prevalence of glutamate receptor subunit 2 (GluR2)-lacking alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is a hallmark of excitotoxicity-related neurodegenerative diseases. Topiramate (TPM) is a structurally novel anticonvulsant with a well-known modulatory effects on AMPA/kainate subtypes of glutamate receptors. The present study aimed at investigating the neuroprotective potential of TPM on 3-nitropropionic acid (3-NP)-induced striatal neurodegeneration and Huntington's disease-like symptoms...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29743604/small-gtpases-and-bar-domain-proteins-regulate-branched-actin-polymerisation-for-clathrin-and-dynamin-independent-endocytosis
#3
Mugdha Sathe, Gayatri Muthukrishnan, James Rae, Andrea Disanza, Mukund Thattai, Giorgio Scita, Robert G Parton, Satyajit Mayor
Using real-time TIRF microscopy imaging, we identify sites of clathrin and dynamin-independent CLIC/GEEC (CG) endocytic vesicle formation. This allows spatio-temporal localisation of known molecules affecting CG endocytosis; GBF1 (a GEF for ARF1), ARF1 and CDC42 which appear sequentially over 60 s, preceding scission. In an RNAi screen for BAR domain proteins affecting CG endocytosis, IRSp53 and PICK1, known interactors of CDC42 and ARF1, respectively, were selected. Removal of IRSp53, a negative curvature sensing protein, abolishes CG endocytosis...
May 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29496607/a-novel-modelling-mechanism-of-pael-receptor-and-gabarapl2-interaction-involved-in-parkinson-s-disease
#4
Priyanka Dutta, Leila Dargahi, Kara E O'Connell, Ashini Bolia, Banu Ozkan, Andreas W Sailer, Kumlesh K Dev
Parkin associated endothelin like receptor (PAELR) is G-protein coupled and ubiquitinated by parkin, promoting its degradation. In autosomal recessive Parkinson's disease, mutations in parkin lead to PAELR aggregation in the endoplasmic reticulum (ER), ER stress, neurotoxicity and cell death. We have identified previously that the protein kinase C interacting protein (PICK1) interacts with and regulates the expression and cell toxicity of PAELR. Here, we experimentally identify and provide in-silico modelling of a novel interaction between PAELR and GABARAPL2 (γ-aminobutyrate type A receptor associated protein like 2), which is an autophagosome-specific Ub-like protein implicated in vesicle trafficking and autophagy...
April 23, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29471107/pick1-deficiency-exacerbates-sepsis-associated-acute-lung-injury-and-impairs-glutathione-synthesis-via-reduction-of-xct
#5
Meizi Qian, Yingying Lou, Yixiu Wang, Minyuan Zhang, Qun Jiang, Yunchang Mo, Kunyuan Han, Shenhui Jin, Qinxue Dai, Yulong Yu, Zhen Wang, Junlu Wang
The role of oxidative stress has been well documented in the development of sepsis-induced acute lung injury (ALI). Protein interaction with C-kinase 1 (PICK1) participates in oxidative stress-related neuronal diseases. However, its function in lung infections and inflammatory diseases is not known. We therefore sought to investigate whether PICK1 is involved in sepsis-induced ALI. Cecal ligation and puncture (CLP) was performed in anesthetized wild type (WT) and PICK1 knock out (KO, PICK1-/- ) mice with C57BL/6 background...
April 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29305867/binding-of-pick1-pdz-domain-with-calcineurin-b-regulates-osteoclast-differentiation
#6
Yuya Kamano, Jun Watanabe, Tsutomu Iida, Takeru Kondo, Hiroko Okawa, Hirofumi Yatani, Makio Saeki, Hiroshi Egusa
The calcineurin/nuclear factor of activated T cell (NFAT) signaling pathway plays a major role in osteoclast differentiation; however, the proteins that react with the calcineurin-NFAT complex in osteoclasts to regulate osteoclastogenesis remain unclear. Here, we present evidence that PICK1 also positively regulates calcineurin B in osteoclasts to activate NFAT to promote osteoclastogenesis. mRNA and protein expression of PICK1 in murine primary bone marrow macrophages (BMMs) was significantly increased during RANKL-induced osteoclast differentiation...
January 29, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29298842/pick1-is-essential-for-insulin-production-and-the-maintenance-of-glucose-homeostasis
#7
Jia Li, Zhuo Mao, Jiandong Huang, Jun Xia
Protein interacting with C-kinase 1 (PICK1) is a peripheral membrane protein that controls insulin granule formation, trafficking, and maturation in INS-1E cells. However, global Pick1 -knockout mice showed only a subtle diabetes-like phenotype. This raises the possibility that compensatory effects from tissues other than pancreatic beta cells may obscure the effects of insulin deficiency. To explore the role of PICK1 in pancreatic islets, we generated mice harboring a conditional Pick1 allele in a C57BL/6J background...
March 1, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29280296/lock-and-chop-a-novel-method-for-the-generation-of-a-pick1-pdz-domain-and-piperidine-based-inhibitor-co-crystal-structure
#8
Douglas J Marcotte, Jean-Christophe Hus, Charles C Banos, Craig Wildes, Robert Arduini, Chris Bergeron, Catherine A Hession, Darren P Baker, Edward Lin, Kevin M Guckian, Anthone W Dunah, Laura F Silvian
The membrane protein interacting with kinase C1 (PICK1) plays a trafficking role in the internalization of neuron receptors such as the amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor. Reduction of surface AMPA type receptors on neurons reduces synaptic communication leading to cognitive impairment in progressive neurodegenerative diseases such as Alzheimer disease. The internalization of AMPA receptors is mediated by the PDZ domain of PICK1 which binds to the GluA2 subunit of AMPA receptors and targets the receptor for internalization through endocytosis, reducing synaptic communication...
March 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29115485/effect-of-willed-movement-training-on-neurorehabilitation-after-focal-cerebral-ischemia-and-on-the-neural-plasticity-associated-signaling-pathway
#9
Zhi-Wen Zhou, Qi-Dong Yang, Qing-Ping Tang, Jie Yang, Rong-Jing Guo, Wen Jiang
Neurorehabilitation training is a therapeutic intervention for the loss of neural function induced by focal cerebral ischemia, however, the effect varies depending on the neurorehabilitation exercises. Willed movement (WM) training is defined as task‑oriented training, which increases enthusiasm of patients to accomplish a specific task. The current study was performed to the evaluate effect of WM training on neurorehabilitation following focal cerebral ischemia, and further investigate the influence on neural plasticity‑associated signaling pathway...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29065458/human-globozoospermia-related-gene-spata16-is-required-for-sperm-formation-revealed-by-crispr-cas9-mediated-mouse-models
#10
Yoshitaka Fujihara, Asami Oji, Tamara Larasati, Kanako Kojima-Kita, Masahito Ikawa
A recent genetic analysis of infertile globozoospermic patients identified causative mutations in three genes: a protein interacting with C kinase 1 ( PICK1 ), dpy 19-like 2 ( DPY19L2 ), and spermatogenesis associated 16 ( SPATA16 ). Although mouse models have clarified the physiological functions of Pick1 and Dpy19l2 during spermatogenesis, Spata16 remains to be determined. Globozoospermic patients carried a homozygous point mutation in SPATA16 at 848G→A/R283Q. We generated CRISPR/Cas9-mediated mutant mice with the same amino acid substitution in the fourth exon of Spata16 to analyze the mutation site at R284Q, which corresponded with R283Q of mutated human SPATA16...
October 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28968657/pharmacological-modulation-of-ampar-rescues-intellectual-disability-like-phenotype-in-tm4sf2-y-mice
#11
Luca Murru, Elena Vezzoli, Anna Longatti, Luisa Ponzoni, Andrea Falqui, Alessandra Folci, Edoardo Moretto, Veronica Bianchi, Daniela Braida, Mariaelvina Sala, Patrizia D'Adamo, Silvia Bassani, Maura Francolini, Maria Passafaro
Intellectual disability affects 2-3% of the world's population and typically begins during childhood, causing impairments in social skills and cognitive abilities. Mutations in the TM4SF2 gene, which encodes the TSPAN7 protein, cause a severe form of intellectual disability, and currently, no therapy is able to ameliorate this cognitive impairment. We previously reported that, in cultured neurons, shRNA-mediated down-regulation of TSPAN7 affects AMPAR trafficking by enhancing PICK1-GluA2 interaction, thereby increasing the intracellular retention of AMPAR...
August 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28951554/endocytosis-and-lysosomal-degradation-of-glua2-3-ampars-in-response-to-oxygen-glucose-deprivation-in-hippocampal-but-not-cortical-neurons
#12
Zsombor Koszegi, Maria Fiuza, Jonathan G Hanley
Global cerebral ischemia results in oxygen and glucose deprivation (OGD) and consequent delayed cell death of vulnerable neurons, with hippocampal CA1 neurons more vulnerable than cortical neurons. Most AMPA receptors (AMPARs) are heteromeric complexes of subunits GluA1/GluA2 or GluA2/GluA3, and the presence of GluA2 renders AMPARs Ca(2+)-impermeable. In hippocampal CA1 neurons, OGD causes the synaptic expression of GluA2-lacking Ca(2+)-permeable AMPARs, contributing to toxic Ca(2+) influx. The loss of synaptic GluA2 is caused by rapid trafficking of GluA2-containing AMPARs from the cell surface, followed by a delayed reduction in GluA2 mRNA expression...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904854/protein-kinase-c-regulates-ampa-receptor-auxiliary-protein-shisa9-ckamp44-through-interactions-with-neuronal-scaffold-pick1
#13
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
https://www.readbyqxmd.com/read/28888867/pick1-facilitates-lasting-reduction-in-glua2-concentration-in-the-hippocampus-during-chronic-epilepsy
#14
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 (GluA2) hypothesis states that following a neurological insult such as an epileptic seizure, the AMPA receptor subunit GluR2 protein is downregulated. This increases the likelihood of the formation of GluR2-lacking, calcium-permeable AMPA receptor which might further enhance the toxicity of the neurotransmitter, glutamate...
August 31, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28867899/homology-modeling-and-protein-interaction-map-of-chrna7-neurogenesis-protein
#15
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
https://www.readbyqxmd.com/read/28855251/pick1-regulates-ampa-receptor-endocytosis-via-direct-interactions-with-ap2-%C3%AE-appendage-and-dynamin
#16
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...
October 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28731156/protein-interacting-with-c%C3%A2-kinase-1-modulates-exocytosis-and-katp-conductance-in-pancreatic-%C3%AE-cells
#17
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
https://www.readbyqxmd.com/read/28697177/the-tgf-%C3%AE-signalling-negative-regulator-pick1-represses-prostate-cancer-metastasis-to-bone
#18
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
https://www.readbyqxmd.com/read/28507309/pick1-genetic-variation-and-cognitive-function-in-patients-with-schizophrenia
#19
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
https://www.readbyqxmd.com/read/28404816/the-pick1-ca-2-sensor-modulates-n-methyl-d-aspartate-nmda-receptor-dependent-microrna-mediated-translational-repression-in-neurons
#20
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
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