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  1. Article: Editorial: The role of trafficking in synaptic development, maintenance, and plasticity.

    Hoerndli, Frederic J / Kurshan, Peri T / Anggono, Victor

    Frontiers in cellular neuroscience

    2024  Volume 18, Page(s) 1362676

    Language English
    Publishing date 2024-01-10
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2024.1362676
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  2. Article ; Online: Characterization of the intracellular neurexin interactome by in vivo proximity ligation suggests its involvement in presynaptic actin assembly.

    Schaan Profes, Marcos / Tiroumalechetty, Araven / Patel, Neel / Lauar, Stephanie S / Sidoli, Simone / Kurshan, Peri T

    PLoS biology

    2024  Volume 22, Issue 1, Page(s) e3002466

    Abstract: Neurexins are highly spliced transmembrane cell adhesion molecules that bind an array of partners via their extracellular domains. However, much less is known about the signaling pathways downstream of neurexin's largely invariant intracellular domain ( ... ...

    Abstract Neurexins are highly spliced transmembrane cell adhesion molecules that bind an array of partners via their extracellular domains. However, much less is known about the signaling pathways downstream of neurexin's largely invariant intracellular domain (ICD). Caenorhabditis elegans contains a single neurexin gene that we have previously shown is required for presynaptic assembly and stabilization. To gain insight into the signaling pathways mediating neurexin's presynaptic functions, we employed a proximity ligation method, endogenously tagging neurexin's intracellular domain with the promiscuous biotin ligase TurboID, allowing us to isolate adjacent biotinylated proteins by streptavidin pull-down and mass spectrometry. We compared our experimental strain to a control strain in which neurexin, endogenously tagged with TurboID, was dispersed from presynaptic active zones by the deletion of its C-terminal PDZ-binding motif. Selection of this control strain, which differs from the experimental strain only in its synaptic localization, was critical to identifying interactions specifically occurring at synapses. Using this approach, we identified both known and novel intracellular interactors of neurexin, including active zone scaffolds, actin-binding proteins (including almost every member of the Arp2/3 complex), signaling molecules, and mediators of RNA trafficking, protein synthesis and degradation, among others. Characterization of mutants for candidate neurexin interactors revealed that they recapitulate aspects of the nrx-1(-) mutant phenotype, suggesting they may be involved in neurexin signaling. Finally, to investigate a possible role for neurexin in local actin assembly, we endogenously tagged its intracellular domain with actin depolymerizing and sequestering peptides (DeActs) and found that this led to defects in active zone assembly. Together, these results suggest neurexin's intracellular domain may be involved in presynaptic actin-assembly, and furthermore highlight a novel approach to achieving high specificity for in vivo proteomics experiments.
    MeSH term(s) Animals ; Actins ; Neurexins ; Microfilament Proteins ; Actin-Related Protein 2-3 Complex ; Caenorhabditis elegans/genetics ; Cell Adhesion Molecules, Neuronal ; Caenorhabditis elegans Proteins/genetics
    Chemical Substances Actins ; Neurexins ; Microfilament Proteins ; Actin-Related Protein 2-3 Complex ; nrx-1 protein, C elegans ; Cell Adhesion Molecules, Neuronal ; Caenorhabditis elegans Proteins
    Language English
    Publishing date 2024-01-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002466
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    Zs.A 6193: Show issues Location:
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  3. Article ; Online: All Talk, No Assembly: Voltage-Gated Calcium Channels Do Not Mediate Active Zone Formation.

    Frankel, Elisa B / Kurshan, Peri T

    Neuron

    2020  Volume 107, Issue 4, Page(s) 593–594

    Abstract: How synapses assemble remains unknown. In this issue of Neuron, Held et al. (2020) demonstrate that ... ...

    Abstract How synapses assemble remains unknown. In this issue of Neuron, Held et al. (2020) demonstrate that Ca
    MeSH term(s) Calcium/metabolism ; Calcium Channels, N-Type/genetics ; Neurons/metabolism ; Synapses/metabolism
    Chemical Substances Calcium Channels, N-Type ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-08-20
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2020.07.028
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    Zs.A 2496: Show issues Location:
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  4. Article ; Online: Synaptogenic pathways.

    Kurshan, Peri T / Shen, Kang

    Current opinion in neurobiology

    2019  Volume 57, Page(s) 156–162

    Abstract: During synaptogenesis, presynaptic and postsynaptic assembly are driven by diverse molecular mechanisms, mediated by intrinsic as well as extrinsic factors. How these processes are initiated and coordinated are open questions. Synapse specificity, or ... ...

    Abstract During synaptogenesis, presynaptic and postsynaptic assembly are driven by diverse molecular mechanisms, mediated by intrinsic as well as extrinsic factors. How these processes are initiated and coordinated are open questions. Synapse specificity, or synaptic partner selection, is widely understood to be determined by the trans-synaptic binding of cell adhesion molecules. However, in vivo evidence that cell adhesion molecules subsequently function to initiate synapse assembly, as initially proposed, is lacking. Here, we present a summary of our current understanding of synaptogenic pathways that mediate presynaptic and postsynaptic assembly and the coordination of these processes.
    MeSH term(s) Neurogenesis ; Synapses
    Language English
    Publishing date 2019-04-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1078046-4
    ISSN 1873-6882 ; 0959-4388
    ISSN (online) 1873-6882
    ISSN 0959-4388
    DOI 10.1016/j.conb.2019.03.005
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    Zs.A 3260: Show issues Location:
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  5. Article: Protein-lipid interactions drive presynaptic assembly upstream of cell adhesion molecules.

    Frankel, Elisa B / Tiroumalechetty, Araven / Henry, Parise S / Su, Zhaoqian / Wu, Yinghao / Kurshan, Peri T

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Textbook models of synaptogenesis position cell adhesion molecules such as neurexin as initiators of synapse assembly. Here we discover a mechanism for presynaptic assembly that occurs prior to neurexin recruitment, while supporting a role for neurexin ... ...

    Abstract Textbook models of synaptogenesis position cell adhesion molecules such as neurexin as initiators of synapse assembly. Here we discover a mechanism for presynaptic assembly that occurs prior to neurexin recruitment, while supporting a role for neurexin in synapse maintenance. We find that the cytosolic active zone scaffold SYD-1 interacts with membrane phospholipids to promote active zone protein clustering at the plasma membrane, and subsequently recruits neurexin to stabilize those clusters. Employing molecular dynamics simulations to model intrinsic interactions between SYD-1 and lipid bilayers followed by
    Language English
    Publishing date 2023-11-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.17.567618
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  6. Article ; Online: C. elegans

    Krout, Mia / Oh, Kelly H / Xiong, Ame / Frankel, Elisa B / Kurshan, Peri T / Kim, Hongkyun / Richmond, Janet E

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 21, Page(s) e2220856120

    Abstract: Synaptic transmission requires the coordinated activity of multiple synaptic proteins that are localized at the active zone (AZ). We previously identified ... ...

    Abstract Synaptic transmission requires the coordinated activity of multiple synaptic proteins that are localized at the active zone (AZ). We previously identified a
    MeSH term(s) Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Carrier Proteins/metabolism ; Neurotransmitter Agents/metabolism ; Presynaptic Terminals/metabolism ; Synaptic Transmission/physiology ; Synaptic Vesicles/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; Carrier Proteins ; Neurotransmitter Agents ; unc-10 protein, C elegans ; CLA-1 protein, C elegans ; Unc-13 protein, C elegans ; rimb-1 protein, C elegans
    Language English
    Publishing date 2023-05-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2220856120
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
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  7. Article ; Online: Dendritic patterning: three-dimensional position determines dendritic avoidance capability.

    Kurshan, Peri T / Shen, Kang

    Current biology : CB

    2012  Volume 22, Issue 6, Page(s) R192–4

    Abstract: Neurons develop mutually exclusive dendritic domains through self-avoidance and tiling mechanisms. Two recent studies establish that this process is dependent on the restriction of dendrites to a two-dimensional plane through interactions with the ... ...

    Abstract Neurons develop mutually exclusive dendritic domains through self-avoidance and tiling mechanisms. Two recent studies establish that this process is dependent on the restriction of dendrites to a two-dimensional plane through interactions with the extracellular matrix.
    MeSH term(s) Animals ; Body Patterning/physiology ; Dendrites/physiology ; Dendrites/ultrastructure ; Drosophila/growth & development ; Drosophila/physiology ; Drosophila/ultrastructure ; Extracellular Matrix/physiology ; Models, Neurological ; Neurogenesis/physiology ; Sensory Receptor Cells/physiology ; Sensory Receptor Cells/ultrastructure
    Language English
    Publishing date 2012-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2012.02.017
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  8. Article: Dendritic Patterning: Three-Dimensional Position Determines Dendritic Avoidance Capability

    Kurshan, Peri T / Shen, Kang

    Current biology. 2012 Mar. 20, v. 22, no. 6

    2012  

    Abstract: Neurons develop mutually exclusive dendritic domains through self-avoidance and tiling mechanisms. Two recent studies establish that this process is dependent on the restriction of dendrites to a two-dimensional plane through interactions with the ... ...

    Abstract Neurons develop mutually exclusive dendritic domains through self-avoidance and tiling mechanisms. Two recent studies establish that this process is dependent on the restriction of dendrites to a two-dimensional plane through interactions with the extracellular matrix.
    Keywords dendrites ; digital images ; extracellular matrix ; neurogenesis
    Language English
    Dates of publication 2012-0320
    Size p. R192-R194.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2012.02.017
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  9. Article ; Online: γ-Neurexin and Frizzled Mediate Parallel Synapse Assembly Pathways Antagonized by Receptor Endocytosis.

    Kurshan, Peri T / Merrill, Sean A / Dong, Yongming / Ding, Chen / Hammarlund, Marc / Bai, Jihong / Jorgensen, Erik M / Shen, Kang

    Neuron

    2018  Volume 100, Issue 1, Page(s) 150–166.e4

    Abstract: Synapse formation defines neuronal connectivity and is thus essential for neuronal circuit assembly. Trans-synaptic interactions of cell adhesion molecules are thought to induce synapse assembly. Here we demonstrate that a recently discovered and ... ...

    Abstract Synapse formation defines neuronal connectivity and is thus essential for neuronal circuit assembly. Trans-synaptic interactions of cell adhesion molecules are thought to induce synapse assembly. Here we demonstrate that a recently discovered and conserved short form of neurexin, γ-neurexin, which lacks canonical extracellular domains, is nonetheless sufficient to promote presynaptic assembly in the nematode C. elegans. γ- but not α-neurexin is required for assembling active zone components, recruiting synaptic vesicles, and clustering calcium channels at release sites to promote evoked synaptic transmission. Furthermore, we find that neurexin functions in parallel with the transmembrane receptor Frizzled, as the absence of both proteins leads to an enhanced phenotype-the loss of most synapses. Frizzled's pro-synaptogenic function is independent of its ligand, Wnt. Wnt binding instead eliminates synapses by inducing Frizzled's endocytosis and the downregulation of neurexin. These results reveal how pro- and anti-synaptogenic factors converge to precisely sculpt circuit formation in vivo.
    MeSH term(s) Animals ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/metabolism ; Cell Adhesion Molecules, Neuronal/metabolism ; Endocytosis/physiology ; Frizzled Receptors/metabolism ; Motor Neurons/metabolism ; Neurogenesis/physiology ; Protein Isoforms ; Synapses/metabolism ; Synaptic Transmission/physiology
    Chemical Substances Caenorhabditis elegans Proteins ; Cell Adhesion Molecules, Neuronal ; Frizzled Receptors ; Protein Isoforms ; nrx-1 protein, C elegans
    Language English
    Publishing date 2018-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2018.09.007
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  10. Article ; Online: Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release.

    Xuan, Zhao / Manning, Laura / Nelson, Jessica / Richmond, Janet E / Colón-Ramos, Daniel A / Shen, Kang / Kurshan, Peri T

    eLife

    2017  Volume 6

    Abstract: Active zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens, we isolated a ... ...

    Abstract Active zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens, we isolated a novel
    MeSH term(s) Animals ; Biological Transport ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/physiology ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/physiology ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/physiology ; Presynaptic Terminals/physiology ; Synaptic Vesicles/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/physiology
    Chemical Substances CLA-1 protein, C elegans ; Caenorhabditis elegans Proteins ; Nerve Tissue Proteins ; Vesicular Transport Proteins
    Language English
    Publishing date 2017-11-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.29276
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