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  1. Article ; Online: In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation

    Erin F. Spence / Shataakshi Dube / Akiyoshi Uezu / Margaret Locke / Erik J. Soderblom / Scott H. Soderling

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 16

    Abstract: The internal molecular mechanisms that underlie excitatory synaptogenesis remain poorly characterized. This study utilizes a chemogenetic approach, in vivo biotin identification (iBioID), to discover previously uncharacterized proteins at nascent ... ...

    Abstract The internal molecular mechanisms that underlie excitatory synaptogenesis remain poorly characterized. This study utilizes a chemogenetic approach, in vivo biotin identification (iBioID), to discover previously uncharacterized proteins at nascent synapses. CARMIL3 is identified as a cytoskeletal protein that facilitates spine maturation and AMPAR recruitment.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation

    Erin F. Spence / Shataakshi Dube / Akiyoshi Uezu / Margaret Locke / Erik J. Soderblom / Scott H. Soderling

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 16

    Abstract: The internal molecular mechanisms that underlie excitatory synaptogenesis remain poorly characterized. This study utilizes a chemogenetic approach, in vivo biotin identification (iBioID), to discover previously uncharacterized proteins at nascent ... ...

    Abstract The internal molecular mechanisms that underlie excitatory synaptogenesis remain poorly characterized. This study utilizes a chemogenetic approach, in vivo biotin identification (iBioID), to discover previously uncharacterized proteins at nascent synapses. CARMIL3 is identified as a cytoskeletal protein that facilitates spine maturation and AMPAR recruitment.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice

    Akiyoshi Uezu / Erin Hisey / Yoshihiko Kobayashi / Yudong Gao / Tyler WA Bradshaw / Patrick Devlin / Ramona Rodriguiz / Purushothama Rao Tata / Scott Soderling

    eLife, Vol

    2019  Volume 8

    Abstract: Human mutations in the dystroglycan complex (DGC) result in not only muscular dystrophy but also cognitive impairments. However, the molecular architecture critical for the synaptic organization of the DGC in neurons remains elusive. Here, we report ... ...

    Abstract Human mutations in the dystroglycan complex (DGC) result in not only muscular dystrophy but also cognitive impairments. However, the molecular architecture critical for the synaptic organization of the DGC in neurons remains elusive. Here, we report Inhibitory Synaptic protein 1 (InSyn1) is a critical component of the DGC whose loss alters the composition of the GABAergic synapses, excitatory/inhibitory balance in vitro and in vivo, and cognitive behavior. Association of InSyn1 with DGC subunits is required for InSyn1 synaptic localization. InSyn1 null neurons also show a significant reduction in DGC and GABA receptor distribution as well as abnormal neuronal network activity. Moreover, InSyn1 null mice exhibit elevated neuronal firing patterns in the hippocampus and deficits in fear conditioning memory. Our results support the dysregulation of the DGC at inhibitory synapses and altered neuronal network activity and specific cognitive tasks via loss of a novel component, InSyn1.
    Keywords GABA ; inhibitory synapse ; dystrophin/dystroglycan complex ; hippocampus ; InSyn1 ; memory ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Peptide array X-linking (PAX)

    Hirokazu Okada / Akiyoshi Uezu / Erik J Soderblom / M Arthur Moseley / Frank B Gertler / Scott H Soderling

    PLoS ONE, Vol 7, Iss 5, p e

    a new peptide-protein identification approach.

    2012  Volume 37035

    Abstract: Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. ... ...

    Abstract Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. Array-formatted bait peptides containing an amino acid-derived cross-linker are photo-induced to crosslink with interacting proteins from lysates of interest. Indirect associations are removed by high stringency washes under denaturing conditions. Covalently trapped proteins are subsequently identified by LC-MS/MS and screened by cluster analysis and domain scanning. We apply this methodology to peptides with different proline-containing consensus sequences and show successful identifications from brain lysates of known and novel proteins containing polyproline motif-binding domains such as EH, EVH1, SH3, WW domains. These results suggest the capacity of arrayed peptide ligands to capture and subsequently identify proteins by mass spectrometry is relatively broad and robust. Additionally, the approach is rapid and applicable to cell or tissue fractions from any source, making the approach a flexible tool for initial protein-protein interaction discovery.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Astrocytes refine cortical connectivity at dendritic spines

    W Christopher Risher / Sagar Patel / Il Hwan Kim / Akiyoshi Uezu / Srishti Bhagat / Daniel K Wilton / Louis-Jan Pilaz / Jonnathan Singh Alvarado / Osman Y Calhan / Debra L Silver / Beth Stevens / Nicole Calakos / Scott H Soderling / Cagla Eroglu

    eLife, Vol

    2014  Volume 3

    Abstract: During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is ... ...

    Abstract During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.
    Keywords synaptogenesi ; thalamocortical ; dendritic spine ; astrocyte ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2014-12-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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