The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Eunjoon Kim - One of the best experts on this subject based on the ideXlab platform.
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iq motif and sec7 domain containing protein 3 iqsec3 interacts with gephyrin to promote inhibitory Synapse formation
Journal of Biological Chemistry, 2016Co-Authors: Gayoung Choii, Hyeyeon Kang, Dongseok Park, Sangmin Jeon, Dongwook Kim, Takuma Mori, Theofilos Papadopoulos, Taesun Yoo, Yeunkum Lee, Eunjoon KimAbstract:Gephyrin is a central scaffold protein that mediates development, function, and plasticity of mammalian inhibitory Synapses by interacting with various inhibitory synaptic proteins. Here, we show that IQSEC3, a guanine nucleotide exchange factor for ARF6, directly interacts with gephyrin, an interaction that is critical for the inhibitory Synapse localization of IQSEC3. Overexpression of IQSEC3 increases inhibitory, but not Excitatory, Synapse density in a guanine nucleotide exchange factor activity-dependent manner. Conversely, knockdown of IQSEC3 decreases size of gephyrin cluster without altering gephyrin puncta density. Collectively, these data reveal that IQSEC3 acts together with gephyrin to regulate inhibitory Synapse development.
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trans synaptic adhesions between netrin g ligand 3 ngl 3 and receptor tyrosine phosphatases lar protein tyrosine phosphatase δ ptpδ and ptpσ via specific domains regulate Excitatory Synapse formation
Journal of Biological Chemistry, 2010Co-Authors: Seokkyu Kwon, Jooyeon Woo, Hyun Kim, Soo Young Kim, Eunjoon KimAbstract:Synaptic cell adhesion molecules regulate various steps of Synapse formation. The trans-synaptic adhesion between postsynaptic NGL-3 (for netrin-G ligand-3) and presynaptic LAR (for leukocyte antigen-related) regulates Excitatory Synapse formation in a bidirectional manner. However, little is known about the molecular details of the NGL-3-LAR adhesion and whether two additional LAR family proteins, protein-tyrosine phosphatase δ (PTPδ), and PTPσ, also interact with NGL-3 and are involved in Synapse formation. We report here that the leucine-rich repeat (LRR) domain of NGL-3, containing nine LRRs, interacts with the first two fibronectin III (FNIII) domains of LAR to induce bidirectional Synapse formation. Moreover, Gln-96 in the first LRR motif of NGL-3 is critical for LAR binding and induction of presynaptic differentiation. PTPδ and PTPσ also interact with NGL-3 via their first two FNIII domains. These two interactions promote Synapse formation in a different manner; the PTPσ-NGL-3 interaction promotes Synapse formation in a bidirectional manner, whereas the PTPδ-NGL-3 interaction instructs only presynaptic differentiation in a unidirectional manner. mRNAs encoding LAR family proteins display overlapping and differential expression patterns in various brain regions. These results suggest that trans-synaptic adhesion between NGL-3 and the three LAR family proteins regulates Excitatory Synapse formation in shared and distinct neural circuits.
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trans synaptic adhesion between ngl 3 and lar regulates the formation of Excitatory Synapses
Nature Neuroscience, 2009Co-Authors: Jooyeon Woo, Anthone W. Dunah, Morgan Sheng, Seokkyu Kwon, Seungwon Choi, Seho Kim, Jaeran Lee, Eunjoon KimAbstract:Although the receptor tyrosine phosphatase LAR is known to regulate the devolvement of Excitatory Synapse and to direct proper guidance of axons, the extracellular ligand for its activation has remained unknown. This study identifies postsynaptic netrin G-ligand 3 (NGL-3) as the trans-synaptic adhesion ligand of LAR and demonstrates a bidirectional regulation of Excitatory Synapse formation by the LAR/NGL-3 interaction.
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ngl family psd 95 interacting adhesion molecules regulate Excitatory Synapse formation
Nature Neuroscience, 2006Co-Authors: Seho Kim, Jooyeon Woo, Seokkyu Kwon, Hyun Kim, Richard J. Weinberg, Alain C Burette, Hye Sun Chung, Hyun Woo Lee, Karam Kim, Eunjoon KimAbstract:Synaptic cell adhesion molecules (CAMs) regulate Synapse formation through their trans-synaptic and heterophilic adhesion. Here we show that postsynaptic netrin-G ligand (NGL) CAMs associate with netrin-G CAMs in an isoform-specific manner and, through their cytosolic tail, with the abundant postsynaptic scaffold postsynaptic density–95 (PSD-95). Overexpression of NGL-2 in cultured rat neurons increased the number of PSD-95–positive dendritic protrusions. NGL-2 located on heterologous cells or beads induced functional presynaptic differentiation in contacting neurites. Direct aggregation of NGL-2 on the surface membrane of dendrites induced the clustering of Excitatory postsynaptic proteins. Competitive inhibition by soluble NGL-2 reduced the number of Excitatory Synapses. NGL-2 knockdown reduced Excitatory, but not inhibitory, Synapse numbers and currents. These results suggest that NGL regulates the formation of Excitatory Synapses.
Won Mah - One of the best experts on this subject based on the ideXlab platform.
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Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion
Cell Press, 2018Co-Authors: Peng Zhang, Tae-yong Choi, Sook Kyung Park, Hanwool Park, Eun-jae Lee, Dongsoo Lee, Junyeop Daniel Roh, Won Mah, Ryunhee KimAbstract:Synaptic adhesion molecules regulate diverse aspects of Synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3-/-) mice display markedly reduced Excitatory Synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3-/- mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates Excitatory Synapse development and locomotion behavior. SALM3 is a postsynaptic adhesion molecule known to regulate Synapse development, but the underlying mechanism remains unclear. Li et al. find that SALM3 interacts with presynaptic LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) in a splicing-dependent manner. In addition, they show that SALM3-mutant mice display reduced Excitatory Synapse number and hypoactivity. © 2015 The Authors212
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salm4 suppresses Excitatory Synapse development by cis inhibiting trans synaptic salm3 lar adhesion
Nature Communications, 2016Co-Authors: Eunkyung Lie, Tae-yong Choi, Junyeop Daniel Roh, Hyeyeon Kang, Yi Sul Cho, Su Yeon Choi, Ran Noh, Doyoun Kim, Jungyong Nam, Won MahAbstract:Synaptic adhesion molecules regulate various aspects of Synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses Excitatory Synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4(-/-)) mice show increased Excitatory Synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4(-/-) mice (Salm3(-/-); Salm4(-/-)) normalizes the increased Excitatory Synapse number. These results suggest that SALM4 negatively regulates Excitatory Synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion.
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splicing dependent trans synaptic salm3 lar rptp interactions regulate Excitatory Synapse development and locomotion
Cell Reports, 2015Co-Authors: Peng Zhang, Tae-yong Choi, Sook Kyung Park, Hanwool Park, Eun-jae Lee, Dongsoo Lee, Junyeop Daniel Roh, Won Mah, Ryunhee Kim, Yangsik KimAbstract:Synaptic adhesion molecules regulate diverse aspects of Synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3(-/-)) mice display markedly reduced Excitatory Synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3(-/-) mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates Excitatory Synapse development and locomotion behavior.
Cagla Eroglu - One of the best experts on this subject based on the ideXlab platform.
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gabapentin receptor α2δ 1 is a neuronal thrombospondin receptor responsible for Excitatory cns synaptogenesis
Cell, 2009Co-Authors: Chandrani Chakraborty, Nicola J Allen, Cagla Eroglu, Michael W Susman, Nancy A Orourke, Engin Ozkan, Sara B Mulinyawe, Chan-young Park, Douglas S AnnisAbstract:Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS Synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced Synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits Excitatory Synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in Excitatory Synapse formation and suggest that gabapentin may function therapeutically by blocking new Synapse formation.
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gabapentin receptor α2δ 1 is a neuronal thrombospondin receptor responsible for Excitatory cns synaptogenesis
Cell, 2009Co-Authors: Chandrani Chakraborty, Nicola J Allen, Cagla Eroglu, Michael W Susman, Nancy A Orourke, Engin Ozkan, Sara B Mulinyawe, Chan-young Park, Douglas S AnnisAbstract:Summary Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS Synapse formation as α2δ-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of α2δ-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. α2δ-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced Synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to α2δ-1 and powerfully inhibits Excitatory Synapse formation in vitro and in vivo. These findings identify α2δ-1 as a receptor involved in Excitatory Synapse formation and suggest that gabapentin may function therapeutically by blocking new Synapse formation.
Tae-yong Choi - One of the best experts on this subject based on the ideXlab platform.
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Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion
Cell Press, 2018Co-Authors: Peng Zhang, Tae-yong Choi, Sook Kyung Park, Hanwool Park, Eun-jae Lee, Dongsoo Lee, Junyeop Daniel Roh, Won Mah, Ryunhee KimAbstract:Synaptic adhesion molecules regulate diverse aspects of Synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3-/-) mice display markedly reduced Excitatory Synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3-/- mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates Excitatory Synapse development and locomotion behavior. SALM3 is a postsynaptic adhesion molecule known to regulate Synapse development, but the underlying mechanism remains unclear. Li et al. find that SALM3 interacts with presynaptic LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) in a splicing-dependent manner. In addition, they show that SALM3-mutant mice display reduced Excitatory Synapse number and hypoactivity. © 2015 The Authors212
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salm4 suppresses Excitatory Synapse development by cis inhibiting trans synaptic salm3 lar adhesion
Nature Communications, 2016Co-Authors: Eunkyung Lie, Tae-yong Choi, Junyeop Daniel Roh, Hyeyeon Kang, Yi Sul Cho, Su Yeon Choi, Ran Noh, Doyoun Kim, Jungyong Nam, Won MahAbstract:Synaptic adhesion molecules regulate various aspects of Synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses Excitatory Synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4(-/-)) mice show increased Excitatory Synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4(-/-) mice (Salm3(-/-); Salm4(-/-)) normalizes the increased Excitatory Synapse number. These results suggest that SALM4 negatively regulates Excitatory Synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion.
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lrrtm3 regulates Excitatory Synapse development through alternative splicing and neurexin binding
Cell Reports, 2016Co-Authors: Tae-yong Choi, Hyeyeon Kang, Yi Sul Cho, Gayoung Choii, Pavel Uvarov, Dongseok Park, Daun Jeong, Sangmin Jeon, Dongmin Lee, Hyun KimAbstract:The four members of the LRRTM family (LRRTM1-4) are postsynaptic adhesion molecules essential for Excitatory Synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its Excitatory Synapse-promoting activity. Overexpression of either LRRTM3 variant increased Excitatory Synapse density in dentate gyrus (DG) granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in Excitatory Synapse density, Excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for Excitatory Synapse development.
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splicing dependent trans synaptic salm3 lar rptp interactions regulate Excitatory Synapse development and locomotion
Cell Reports, 2015Co-Authors: Peng Zhang, Tae-yong Choi, Sook Kyung Park, Hanwool Park, Eun-jae Lee, Dongsoo Lee, Junyeop Daniel Roh, Won Mah, Ryunhee Kim, Yangsik KimAbstract:Synaptic adhesion molecules regulate diverse aspects of Synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3(-/-)) mice display markedly reduced Excitatory Synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3(-/-) mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates Excitatory Synapse development and locomotion behavior.
Douglas S Annis - One of the best experts on this subject based on the ideXlab platform.
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gabapentin receptor α2δ 1 is a neuronal thrombospondin receptor responsible for Excitatory cns synaptogenesis
Cell, 2009Co-Authors: Chandrani Chakraborty, Nicola J Allen, Cagla Eroglu, Michael W Susman, Nancy A Orourke, Engin Ozkan, Sara B Mulinyawe, Chan-young Park, Douglas S AnnisAbstract:Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS Synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced Synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits Excitatory Synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in Excitatory Synapse formation and suggest that gabapentin may function therapeutically by blocking new Synapse formation.
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gabapentin receptor α2δ 1 is a neuronal thrombospondin receptor responsible for Excitatory cns synaptogenesis
Cell, 2009Co-Authors: Chandrani Chakraborty, Nicola J Allen, Cagla Eroglu, Michael W Susman, Nancy A Orourke, Engin Ozkan, Sara B Mulinyawe, Chan-young Park, Douglas S AnnisAbstract:Summary Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS Synapse formation as α2δ-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of α2δ-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. α2δ-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced Synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to α2δ-1 and powerfully inhibits Excitatory Synapse formation in vitro and in vivo. These findings identify α2δ-1 as a receptor involved in Excitatory Synapse formation and suggest that gabapentin may function therapeutically by blocking new Synapse formation.
