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Mary B Kennedy - One of the best experts on this subject based on the ideXlab platform.
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identification of proteins in the postsynaptic Density Fraction by mass spectrometry
The Journal of Neuroscience, 2000Co-Authors: Randall S Walikonis, Ole Norregaard Jensen, Matthias Mann, William D Provance, John A Mercer, Mary B KennedyAbstract:Our understanding of the organization of postsynaptic signaling systems at excitatory synapses has been aided by the identification of proteins in the postsynaptic Density (PSD) Fraction, a subcellular Fraction enriched in structures with the morphology of PSDs. In this study, we have completed the identification of most major proteins in the PSD Fraction with the use of an analytical method based on mass spectrometry coupled with searching of the protein sequence databases. At least one protein in each of 26 prominent protein bands from the PSD Fraction has now been identified. We found 7 proteins not previously known to be constituents of the PSD Fraction and 24 that had previously been associated with the PSD by other methods. The newly identified proteins include the heavy chain of myosin-Va (dilute myosin), a motor protein thought to be involved in vesicle trafficking, and the mammalian homolog of the yeast septin protein cdc10, which is important for bud formation in yeast. Both myosin-Va and cdc10 are threefold to fivefold enriched in the PSD Fraction over brain homogenates. Immunocytochemical localization of myosin-Va in cultured hippocampal neurons shows that it partially colocalizes with PSD-95 at synapses and is also diffusely localized in cell bodies, dendrites, and axons. Cdc10 has a punctate distribution in cell bodies and dendrites, with some of the puncta colocalizing with PSD-95. The results support a role for myosin-Va in transport of materials into spines and for septins in the formation or maintenance of spines.
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Characterization of Densin-180, a New Brain-Specific Synaptic Protein of the O-Sialoglycoprotein Family
The Journal of Neuroscience, 1996Co-Authors: Michelle L Apperson, Ill Soo Moon, Mary B KennedyAbstract:We purified an abundant protein of apparent molecular mass 180 kDa from the postsynaptic Density Fraction of rat forebrain and obtained amino acid sequences of three tryptic peptides generated from the protein. The sequences were used to design a strategy for cloning the cDNA encoding the protein by polymerase chain reaction. The open reading frame of the cDNA encodes a novel protein of predicted molecular mass 167 kDa. We have named the protein densin-180. Antibodies raised against the predicted amino and carboxyl sequences of densin-180 recognize a 180 kDa band on immunoblots that is enriched in the postsynaptic Density Fraction. Immunocytochemical localization of densin-180 in dissociated hippocampal neuronal cultures shows that the protein is highly concentrated at synapses along dendrites. The message encoding densin-180 is brain specific and is more abundant in forebrain than in cerebellum. The sequence of densin-180 contains 17 leucine-rich repeats, a sialomucin domain, an apparent transmembrane domain, and a PDZ domain. This arrangement of domains is similar to that of several adhesion molecules, in particular GPIbalpha, which mediates binding of platelets to von Willebrand factor. We propose that densin-180 participates in specific adhesion between presynaptic and postsynaptic membranes at glutamatergic synapses.
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the major tyrosine phosphorylated protein in the postsynaptic Density Fraction is n methyl d aspartate receptor subunit 2b
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Ilsoo Moon, Michelle L Apperson, Mary B KennedyAbstract:The postsynaptic Density (PSD) is a specialization of the submembranous cytoskeleton that is visible in the electron microscope on the cytoplasmic face of the postsynaptic membrane. A subcellular Fraction enriched in structures with the morphology of PSDs contains signal-transduction molecules thought to regulate receptor localization and function in the central nervous system. We have purified a prominent tyrosine-phosphorylated glycoprotein of apparent molecular mass 180 kDa, termed PSD-gp180, that is highly enriched in the rat forebrain PSD Fraction. The sequences of four tryptic peptides generated from the protein reveal that it is the 2B subunit of the N-methyl-D-aspartate (NMDA) type glutamate receptor. We have confirmed the identity of PSD-gp180 by showing that it reacts with antibodies raised against a unique fragment of the 2B subunit of the NMDA receptor. We also show that the 2B subunit is the most prominently tyrosine-phosphorylated protein in the PSD Fraction based upon recognition by an anti-phosphotyrosine antibody. Two types of NMDA receptor subunits have been identified by molecular cloning [Nakanishi, S. (1992) Science 258, 597-603]. The single type 1 subunit is expressed throughout the brain and is necessary for formation of the receptor channel. The four type 2 subunits (2A, 2B, 2C, and 2D) are expressed in discrete brain regions, contain unusually long unique C termini, and confer distinct kinetic properties on NMDA receptors that contain them. Our findings suggest that, in the forebrain, NMDA receptor subunit 2B may serve to anchor NMDA receptors at the postsynaptic membrane through its interaction with the PSD. The prominent presence of tyrosine phosphate further suggests that the NMDA receptor may be regulated by tyrosine phosphorylation or that it may participate in signaling through tyrosine phosphorylation and through its ion channel.
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the rat brain postsynaptic Density Fraction contains a homolog of the drosophila discs large tumor suppressor protein
Neuron, 1992Co-Authors: Kyungok Cho, Carol A Hunt, Mary B KennedyAbstract:In CNS synapses, the synaptic junctional complex with associated postsynaptic Density is presumed to contain proteins responsible for adhesion between pre- and postsynaptic membranes and for postsynaptic signal transduction. We have found that a prominent, brain-specific protein (PSD-95) enriched in the postsynaptic Density Fraction from rat brain is highly similar to the Drosophila lethal(1)discs-large-1 (dlg) tumor suppressor protein. The dlg protein is associated with septate junctions in developing flies and contains a guanylate kinase domain that is required for normal control of cell division. The sequence similarity between dlg and PSD-95 suggests that molecular mechanisms critical for growth control in developing organisms may also regulate synapse formation, stabilization, or function in the adult brain.
Mikhail M Ivanov - One of the best experts on this subject based on the ideXlab platform.
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blinded challenge for precision cosmology with large scale structure results from effective field theory for the redshift space galaxy power spectrum
Physical Review D, 2020Co-Authors: Takahiro Nishimichi, Guido Damico, Mikhail M Ivanov, Leonardo Senatore, Marko Simonovic, Masahiro Takada, Matias ZaldarriagaAbstract:An accurate theoretical template for the galaxy power spectrum is key for the success of ongoing and future spectroscopic surveys. We examine to what extent the effective field theory (EFT) of large-scale structure is able to provide such a template and correctly estimate cosmological parameters. To that end, we initiate a blinded challenge to infer cosmological parameters from the redshift-space power spectrum of high-resolution mock catalogs mimicking the BOSS galaxy sample but covering a 100 times larger cumulative volume. This gigantic simulation volume allows us to separate systematic bias due to theoretical modeling from the statistical error due to sample variance. The challenge is to measure three unknown input parameters used in the simulation: the Hubble constant, the matter Density Fraction, and the clustering amplitude. We present analyses done by two independent teams, who have fitted the mock simulation data generated by yet another independent group. This allows us to avoid any confirmation bias by analyzers and to pin down possible tuning of the specific EFT implementations. Both independent teams have recovered the true values of the input parameters within subpercent statistical errors corresponding to the total simulation volume.
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cosmological parameters from the boss galaxy power spectrum
Journal of Cosmology and Astroparticle Physics, 2020Co-Authors: Mikhail M Ivanov, Marko Simonovic, Matias ZaldarriagaAbstract:We present cosmological parameter measurements from the publicly available Baryon Oscillation Spectroscopic Survey (BOSS) data on anisotropic galaxy clustering in Fourier space. Compared to previous studies, our analysis has two main novel features. First, we use a complete perturbation theory model that properly takes into account the non-linear effects of dark matter clustering, short-scale physics, galaxy bias, redshift-space distortions, and large-scale bulk flows. Second, we employ a Markov-Chain Monte-Carlo technique and consistently reevaluate the full power spectrum likelihood as we scan over different cosmologies. Our baseline analysis assumes minimal ΛCDM, varies the neutrino masses within a reasonably tight range, fixes the primordial power spectrum tilt, and uses the big bang nucleosynthesis prior on the physical baryon Density ωb. In this setup, we find the following late-Universe parameters: Hubble constant H0=(67.9± 1.1) km s−1Mpc−1, matter Density Fraction Ωm=0.295± 0.010, and the mass fluctuation amplitude σ8=0.721± 0.043. These parameters were measured directly from the BOSS data and independently of the Planck cosmic microwave background observations. Scanning over the power spectrum tilt or relaxing the other priors do not significantly alter our main conclusions. Finally, we discuss the information content of the BOSS power spectrum and show that it is dominated by the location of the baryon acoustic oscillations and the power spectrum shape. We argue that the contribution of the Alcock-Paczynski effect is marginal in ΛCDM, but becomes important for non-minimal cosmological models.
Matias Zaldarriaga - One of the best experts on this subject based on the ideXlab platform.
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blinded challenge for precision cosmology with large scale structure results from effective field theory for the redshift space galaxy power spectrum
Physical Review D, 2020Co-Authors: Takahiro Nishimichi, Guido Damico, Mikhail M Ivanov, Leonardo Senatore, Marko Simonovic, Masahiro Takada, Matias ZaldarriagaAbstract:An accurate theoretical template for the galaxy power spectrum is key for the success of ongoing and future spectroscopic surveys. We examine to what extent the effective field theory (EFT) of large-scale structure is able to provide such a template and correctly estimate cosmological parameters. To that end, we initiate a blinded challenge to infer cosmological parameters from the redshift-space power spectrum of high-resolution mock catalogs mimicking the BOSS galaxy sample but covering a 100 times larger cumulative volume. This gigantic simulation volume allows us to separate systematic bias due to theoretical modeling from the statistical error due to sample variance. The challenge is to measure three unknown input parameters used in the simulation: the Hubble constant, the matter Density Fraction, and the clustering amplitude. We present analyses done by two independent teams, who have fitted the mock simulation data generated by yet another independent group. This allows us to avoid any confirmation bias by analyzers and to pin down possible tuning of the specific EFT implementations. Both independent teams have recovered the true values of the input parameters within subpercent statistical errors corresponding to the total simulation volume.
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cosmological parameters from the boss galaxy power spectrum
Journal of Cosmology and Astroparticle Physics, 2020Co-Authors: Mikhail M Ivanov, Marko Simonovic, Matias ZaldarriagaAbstract:We present cosmological parameter measurements from the publicly available Baryon Oscillation Spectroscopic Survey (BOSS) data on anisotropic galaxy clustering in Fourier space. Compared to previous studies, our analysis has two main novel features. First, we use a complete perturbation theory model that properly takes into account the non-linear effects of dark matter clustering, short-scale physics, galaxy bias, redshift-space distortions, and large-scale bulk flows. Second, we employ a Markov-Chain Monte-Carlo technique and consistently reevaluate the full power spectrum likelihood as we scan over different cosmologies. Our baseline analysis assumes minimal ΛCDM, varies the neutrino masses within a reasonably tight range, fixes the primordial power spectrum tilt, and uses the big bang nucleosynthesis prior on the physical baryon Density ωb. In this setup, we find the following late-Universe parameters: Hubble constant H0=(67.9± 1.1) km s−1Mpc−1, matter Density Fraction Ωm=0.295± 0.010, and the mass fluctuation amplitude σ8=0.721± 0.043. These parameters were measured directly from the BOSS data and independently of the Planck cosmic microwave background observations. Scanning over the power spectrum tilt or relaxing the other priors do not significantly alter our main conclusions. Finally, we discuss the information content of the BOSS power spectrum and show that it is dominated by the location of the baryon acoustic oscillations and the power spectrum shape. We argue that the contribution of the Alcock-Paczynski effect is marginal in ΛCDM, but becomes important for non-minimal cosmological models.
Shogo Endo - One of the best experts on this subject based on the ideXlab platform.
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characterization of mrna species that are associated with postsynaptic Density Fraction by gene chip microarray analysis
Neuroscience Research, 2007Co-Authors: Tatsuo Suzuki, Qing Bao Tian, Junro Kuromitsu, Takatoshi Kawai, Shogo EndoAbstract:Abstract We previously reported the partial identification by random sequencing of mRNA species that are associated with the postsynaptic Density (PSD) Fraction prepared from the rat forebrain [Tian et al., 1999. Mol. Brain Res. 72, 147–157]. We report here further characterization by gene chip analysis of the PSD Fraction-associated mRNAs, which were prepared in the presence of RNase inhibitor. We found that mRNAs encoding various postsynaptic proteins, such as channels, receptors for neurotransmitters and neuromodulators, proteins involved in signaling, scaffold and adaptor proteins and cytoskeletal proteins, were highly concentrated in the PSD Fraction, whereas those encoding housekeeping proteins, such as enzymes in the glycolytic pathway, were not. We extracted ∼1900 mRNA species that were highly concentrated in the PSD Fraction. mRNAs related to certain neuronal diseases were also enriched in the PSD Fraction. We also constructed a cDNA library using the PSD Fraction-associated mRNAs as templates, and identified 1152 randomly selected clones by sequencing. Our data suggested that the PSD Fraction-associated mRNAs are a very useful resource, in which a number of as yet uncharacterized mRNAs are concentrated. Identification and functional characterization of them are essential for complete understanding of synaptic function.
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Characterization of mRNA species that are associated with postsynaptic Density Fraction by gene chip microarray analysis
Neuroscience research, 2006Co-Authors: Tatsuo Suzuki, Qing Bao Tian, Junro Kuromitsu, Takatoshi Kawai, Shogo EndoAbstract:We previously reported the partial identification by random sequencing of mRNA species that are associated with the postsynaptic Density (PSD) Fraction prepared from the rat forebrain [Tian et al., 1999. Mol. Brain Res. 72, 147-157]. We report here further characterization by gene chip analysis of the PSD Fraction-associated mRNAs, which were prepared in the presence of RNase inhibitor. We found that mRNAs encoding various postsynaptic proteins, such as channels, receptors for neurotransmitters and neuromodulators, proteins involved in signaling, scaffold and adaptor proteins and cytoskeletal proteins, were highly concentrated in the PSD Fraction, whereas those encoding housekeeping proteins, such as enzymes in the glycolytic pathway, were not. We extracted approximately 1900 mRNA species that were highly concentrated in the PSD Fraction. mRNAs related to certain neuronal diseases were also enriched in the PSD Fraction. We also constructed a cDNA library using the PSD Fraction-associated mRNAs as templates, and identified 1152 randomly selected clones by sequencing. Our data suggested that the PSD Fraction-associated mRNAs are a very useful resource, in which a number of as yet uncharacterized mRNAs are concentrated. Identification and functional characterization of them are essential for complete understanding of synaptic function.
Tatsuo Suzuki - One of the best experts on this subject based on the ideXlab platform.
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synarfgef is a guanine nucleotide exchange factor for arf6 and localizes preferentially at post synaptic specializations of inhibitory synapses
Journal of Neurochemistry, 2011Co-Authors: Masahiro Fukaya, Tatsuo Suzuki, Akifumi Kamata, Yoshinobu Hara, Hideaki Tamaki, Osamu Katsumata, Naoki Ito, Shinichi Takeda, Yutaka Hata, Masahiko WatanabeAbstract:SynArfGEF, also known as BRAG3 or IQSEC3, is a member of the brefeldin A-resistant Arf-GEF/IQSEC family and was originally identified by screening for mRNA species associated with the post-synaptic Density Fraction. In this study, we demonstrate that synArfGEF activates Arf6, using Arf pull down and transferrin incorporation assays. Immunohistochemical analysis reveals that synArfGEF is present in somata and dendrites as puncta in close association with inhibitory synapses, whereas immunoelectron microscopic analysis reveals that synArfGEF localizes preferentially at post-synaptic specializations of symmetric synapses. Using yeast two-hybrid and pull down assays, we show that synArfGEF is able to bind utrophin/dystrophin and S-SCAM/MAGI-2 scaffolding proteins that localize at inhibitory synapses. Double immunostaining reveals that synArfGEF co-localizes with dystrophin and S-SCAM in cultured hippocampal neurons and cerebellar cortex, respectively. Both β-dystroglycan and S-SCAM were immunoprecipitated from brain lysates using anti-synArfGEF IgG. Taken together, these findings suggest that synArfGEF functions as a novel regulator of Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM.
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characterization of mrna species that are associated with postsynaptic Density Fraction by gene chip microarray analysis
Neuroscience Research, 2007Co-Authors: Tatsuo Suzuki, Qing Bao Tian, Junro Kuromitsu, Takatoshi Kawai, Shogo EndoAbstract:Abstract We previously reported the partial identification by random sequencing of mRNA species that are associated with the postsynaptic Density (PSD) Fraction prepared from the rat forebrain [Tian et al., 1999. Mol. Brain Res. 72, 147–157]. We report here further characterization by gene chip analysis of the PSD Fraction-associated mRNAs, which were prepared in the presence of RNase inhibitor. We found that mRNAs encoding various postsynaptic proteins, such as channels, receptors for neurotransmitters and neuromodulators, proteins involved in signaling, scaffold and adaptor proteins and cytoskeletal proteins, were highly concentrated in the PSD Fraction, whereas those encoding housekeeping proteins, such as enzymes in the glycolytic pathway, were not. We extracted ∼1900 mRNA species that were highly concentrated in the PSD Fraction. mRNAs related to certain neuronal diseases were also enriched in the PSD Fraction. We also constructed a cDNA library using the PSD Fraction-associated mRNAs as templates, and identified 1152 randomly selected clones by sequencing. Our data suggested that the PSD Fraction-associated mRNAs are a very useful resource, in which a number of as yet uncharacterized mRNAs are concentrated. Identification and functional characterization of them are essential for complete understanding of synaptic function.
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Characterization of mRNA species that are associated with postsynaptic Density Fraction by gene chip microarray analysis
Neuroscience research, 2006Co-Authors: Tatsuo Suzuki, Qing Bao Tian, Junro Kuromitsu, Takatoshi Kawai, Shogo EndoAbstract:We previously reported the partial identification by random sequencing of mRNA species that are associated with the postsynaptic Density (PSD) Fraction prepared from the rat forebrain [Tian et al., 1999. Mol. Brain Res. 72, 147-157]. We report here further characterization by gene chip analysis of the PSD Fraction-associated mRNAs, which were prepared in the presence of RNase inhibitor. We found that mRNAs encoding various postsynaptic proteins, such as channels, receptors for neurotransmitters and neuromodulators, proteins involved in signaling, scaffold and adaptor proteins and cytoskeletal proteins, were highly concentrated in the PSD Fraction, whereas those encoding housekeeping proteins, such as enzymes in the glycolytic pathway, were not. We extracted approximately 1900 mRNA species that were highly concentrated in the PSD Fraction. mRNAs related to certain neuronal diseases were also enriched in the PSD Fraction. We also constructed a cDNA library using the PSD Fraction-associated mRNAs as templates, and identified 1152 randomly selected clones by sequencing. Our data suggested that the PSD Fraction-associated mRNAs are a very useful resource, in which a number of as yet uncharacterized mRNAs are concentrated. Identification and functional characterization of them are essential for complete understanding of synaptic function.