Jaehoon Shim - Academia.edu (original) (raw)

Papers by Jaehoon Shim

The Journal of Neuroscience, 2012

Long-term facilitation inAplysiais accompanied by the growth of new synaptic connections between ... more Long-term facilitation inAplysiais accompanied by the growth of new synaptic connections between the sensory and motor neurons of the gill-withdrawal reflex. One of the initial steps leading to the growth of these synapses is the internalization, induced by 5-HT, of the transmembrane isoform ofAplysiacell-adhesion molecule (TM–apCAM) from the plasma membrane of sensory neurons (Bailey et al., 1992). However, the mechanisms that govern the internalization of TM–apCAM and how this internalization is coupled to the molecular events that initiate the structural changes are not fully understood. Here, we report that the synthesis of membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], which is known to be mediated by a signaling cascade throughAplysiaSec7 protein (ApSec7) and phosphatidylinositol-4-phosphate 5-kinase type I α (PIP5KIα) is required for both the internalization of TM–apCAM and the initiation of synaptic growth during 5-HT-induced long-term facilitation. Pharmacologi...

Control data of optogenetic inhibition on ACC CaMKII-positive neurons. A, Result of the CaMKII-EY... more Control data of optogenetic inhibition on ACC CaMKII-positive neurons. A, Result of the CaMKII-EYFP-CFA group. There was no light effect before (off: 4.77 ± 0.20 g, on: 4.97 ± 0.15 g; n = 6) or after CFA (off: 2.81 ± 0.22 g, on: 2.90 ± 0.16 g; n = 6). There was only a statistically significant effect of CFA treatment per se (p

Control experiments for locomotion and anxiety. A, Results of the CaMKII-EYFP and CaMKII-ChR2 gro... more Control experiments for locomotion and anxiety. A, Results of the CaMKII-EYFP and CaMKII-ChR2 groups in the open field test (OFT). There was no difference between the two groups in either locomotion (EYFP: 5824 ± 457.6 cm, n = 8; ChR2: 6207 ± 244.8 cm, n = 17; p = 0.4273, Unpaired t test) or time spent in the center (EYFP: 9.17 ± 1.85 %, n = 8; ChR2: 11.27 ± 1.68 %, n = 17; p = 0.4559, Unpaired t test). B, Results of the CaMKII-EYFP and CaMKII-eNpHR groups in the OFT. There was no difference between the two groups in either locomotion (EYFP: 6616 ± 278.4 cm, n = 7; eNpHR: 6043 ± 212.9 cm, n = 12; p = 0.1209, Unpaired t test) or time spent in the center (EYFP: 10.96 ± 2.34 %, n = 7; eNpHR: 10.15 ± 1.35 %, n = 12; p = 0.7488, Unpaired t test). (PNG 28 kb)

Superresolution fluorescence microscopy for 3D reconstruction of thick samples. (PDF 914 kb)

Molecular Brain, 2017

Protein kinase M zeta (PKMζ), a constitutively active, atypical protein kinase C isoform, maintai... more Protein kinase M zeta (PKMζ), a constitutively active, atypical protein kinase C isoform, maintains a high level of expression in the brain after the induction of learning and long-term potentiation (LTP). Further, its overexpression enhances long-term memory and LTP. Thus, multiple lines of evidence suggest a significant role for persistently elevated PKMζ levels in long-term memory. The molecular mechanisms of how synaptic properties are regulated by the increase in PKMζ, however, are still largely unknown. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) mediates most of the fast glutamatergic synaptic transmission in the brain and is known to be critical for the expression of synaptic plasticity and memory. Importance of AMPAR trafficking has been implicated in PKMζ-mediated cellular processes, but the detailed mechanisms, particularly in terms of regulation of AMPAR lateral movement, are not well understood. In the current study, using a single-molecule live imaging technique, we report that the overexpression of PKMζ in hippocampal neurons immobilized GluA2-containing AMPARs, highlighting a potential novel mechanism by which PKMζ may regulate memory and synaptic plasticity.

Molecular brain, Jan 15, 2018

Three-dimensional (3D) reconstruction of thick samples using superresolution fluorescence microsc... more Three-dimensional (3D) reconstruction of thick samples using superresolution fluorescence microscopy remains challenging due to high level of background noise and fast photobleaching of fluorescence probes. We develop superresolution fluorescence microscopy that can reconstruct 3D structures of thick samples with both high localization accuracy and no photobleaching problem. The background noise is reduced by optically sectioning the sample using line-scan confocal microscopy, and the photobleaching problem is overcome by using the DNA-PAINT (Point Accumulation for Imaging in Nanoscale Topography). As demonstrations, we take 3D superresolution images of microtubules of a whole cell, and two-color 3D images of microtubules and mitochondria. We also present superresolution images of chemical synapse of a mouse brain section at different z-positions ranging from 0 μm to 100 μm.

Cell reports, Jan 16, 2018

Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized noc... more Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment.

Scientific reports, Jan 7, 2017

Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptiona... more Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 (SA/SA) knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in ...

Neurobiology of learning and memory, 2017

ADP-ribosylation factors (ARFs) are small guanosine triphosphatases of the Ras superfamily involv... more ADP-ribosylation factors (ARFs) are small guanosine triphosphatases of the Ras superfamily involved in membrane trafficking and regulation of the actin cytoskeleton. Aplysia Sec7 protein (ApSec7), a guanine nucleotide exchange factor for ARF1 and ARF6, induces neurite outgrowth and plays a key role in 5-hydroxyltryptamine-induced neurite growth and synaptic facilitation in Aplysia sensory-motor synapses. However, the specific role of ARF6 signaling on neurite outgrowth in Aplysia neurons has not been examined. In the present study, we cloned Aplysia ARF6 (ApARF6) and revealed that an overexpression of enhanced green fluorescent protein (EGFP)-fused constitutively active ApARF6 (ApARF6-Q67L-EGFP) could induce neurite outgrowth in Aplysia sensory neurons. Further, we observed that ApARF6-induced neurite outgrowth was inhibited by the co-expression of a Sec7 activity-deficient mutant of ApSec7 (ApSec7-E159K). The pleckstrin homology domain of ApSec7 may bind to active ApARF6 at the pla...

Molecular brain, Oct 22, 2016

Two pharmacologically distinct types of local protein synthesis are required for synapse- specifi... more Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF. ApCPEB4 which we have named after its mammalian CPEB4-like homolog lacks a prion-like domain, is responsive to 5-hydroxytryptamine, and is translated (but not transcribed) in an emetine-sensitive, rapamycin-insensitive, and PKA-dependent manner. The ApCPEB4 binds to different target RNAs than does ApCPEB. Knock-down of ApCPEB4 blocked the induction of LTF, whereas overexpression of ApCPEB4 reduces the thresh...

Proceedings of the National Academy of Sciences, 2012

The consolidation of long-term memory for sensitization and synaptic facilitation in Aplysia requ... more The consolidation of long-term memory for sensitization and synaptic facilitation in Aplysia requires synthesis of new mRNA including the immediate early gene Aplysia CCAAT enhancer-binding protein ( ApC/EBP ). After the rapid induction of ApC/EBP expression in response to repeated treatments of 5-hydroxytryptamine (5-HT), ApC/EBP mRNA is temporarily expressed in sensory neurons of sensory-to-motor synapses. However, the molecular mechanism underlying the rapid degradation of ApC/EBP transcript is not known. Here, we cloned an AU-rich element (ARE)-binding protein, ApAUF1, which functions as a destabilizing factor for ApC/EBP mRNA. ApAUF1 was found to bind to the 3′ UTR of ApC/EBP mRNA that contains AREs and subsequently reduces the expression of ApC/EBP 3′ UTR-containing reporter genes. Moreover, overexpression of ApAUF1 inhibited the induction of ApC/EBP mRNA in sensory neurons and also impaired long-term facilitation of sensory-to-motor synapses by repetitive 5-HT treatments. The...

Proceedings of the National Academy of Sciences, 2012

The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval... more The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia , and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron sy...

Science (New York, N.Y.), Jan 3, 2010

Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the cen... more Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the central nervous system, including spinal cord and cortex. Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain. We found that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKMζ in the ACC, and inhibiting PKMζ by a selective inhibitor, ζ-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKMζ in the ACC acts to maintain neuropathic pain. PKMζ could thus be a new therapeutic target for treating chronic pain.

Animal Cells and Systems, 2013

One neuron receives thousands of inputs through synapses, which contain distinct molecular compon... more One neuron receives thousands of inputs through synapses, which contain distinct molecular components and display different properties. It has been a major challenge in neuroscience to understand the development and function of specific synapses. One of the critical molecules involved in shaping synapse-specific properties is the cell adhesion molecule (CAM). Remarkable numbers of studies have shown the importance of cell-cell interaction mediated by various types of CAMs in defining synapse-specific function. Here, we summarize current understanding of CAMs playing a pivotal role in constructing neural circuits and guiding synapse-specific plasticity. Different CAMs localized at specific synapses are discussed in this review.

Scientific reports, Jan 10, 2016

Cell-permeable proteins are emerging as unconventional regulators of signal transduction and prov... more Cell-permeable proteins are emerging as unconventional regulators of signal transduction and providing a potential for therapeutic applications. However, only a few of them are identified and studied in detail. We identify a novel cell-permeable protein, mouse LLP homolog (mLLP), and uncover its roles in regulating neural development. We found that mLLP is strongly expressed in developing nervous system and that mLLP knockdown or overexpression during maturation of cultured neurons affected the neuronal growth and synaptic transmission. Interestingly, extracellular addition of mLLP protein enhanced dendritic arborization, demonstrating the non-cell-autonomous effect of mLLP. Moreover, mLLP interacts with CCCTC-binding factor (CTCF) as well as transcriptional machineries and modulates gene expression involved in neuronal growth. Together, these results illustrate the characteristics and roles of previously unknown cell-permeable protein mLLP in modulating neural development.

The Journal of Neuroscience, 2012

Long-term facilitation inAplysiais accompanied by the growth of new synaptic connections between ... more Long-term facilitation inAplysiais accompanied by the growth of new synaptic connections between the sensory and motor neurons of the gill-withdrawal reflex. One of the initial steps leading to the growth of these synapses is the internalization, induced by 5-HT, of the transmembrane isoform ofAplysiacell-adhesion molecule (TM–apCAM) from the plasma membrane of sensory neurons (Bailey et al., 1992). However, the mechanisms that govern the internalization of TM–apCAM and how this internalization is coupled to the molecular events that initiate the structural changes are not fully understood. Here, we report that the synthesis of membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], which is known to be mediated by a signaling cascade throughAplysiaSec7 protein (ApSec7) and phosphatidylinositol-4-phosphate 5-kinase type I α (PIP5KIα) is required for both the internalization of TM–apCAM and the initiation of synaptic growth during 5-HT-induced long-term facilitation. Pharmacologi...

Control data of optogenetic inhibition on ACC CaMKII-positive neurons. A, Result of the CaMKII-EY... more Control data of optogenetic inhibition on ACC CaMKII-positive neurons. A, Result of the CaMKII-EYFP-CFA group. There was no light effect before (off: 4.77 ± 0.20 g, on: 4.97 ± 0.15 g; n = 6) or after CFA (off: 2.81 ± 0.22 g, on: 2.90 ± 0.16 g; n = 6). There was only a statistically significant effect of CFA treatment per se (p

Control experiments for locomotion and anxiety. A, Results of the CaMKII-EYFP and CaMKII-ChR2 gro... more Control experiments for locomotion and anxiety. A, Results of the CaMKII-EYFP and CaMKII-ChR2 groups in the open field test (OFT). There was no difference between the two groups in either locomotion (EYFP: 5824 ± 457.6 cm, n = 8; ChR2: 6207 ± 244.8 cm, n = 17; p = 0.4273, Unpaired t test) or time spent in the center (EYFP: 9.17 ± 1.85 %, n = 8; ChR2: 11.27 ± 1.68 %, n = 17; p = 0.4559, Unpaired t test). B, Results of the CaMKII-EYFP and CaMKII-eNpHR groups in the OFT. There was no difference between the two groups in either locomotion (EYFP: 6616 ± 278.4 cm, n = 7; eNpHR: 6043 ± 212.9 cm, n = 12; p = 0.1209, Unpaired t test) or time spent in the center (EYFP: 10.96 ± 2.34 %, n = 7; eNpHR: 10.15 ± 1.35 %, n = 12; p = 0.7488, Unpaired t test). (PNG 28 kb)

Superresolution fluorescence microscopy for 3D reconstruction of thick samples. (PDF 914 kb)

Molecular Brain, 2017

Protein kinase M zeta (PKMζ), a constitutively active, atypical protein kinase C isoform, maintai... more Protein kinase M zeta (PKMζ), a constitutively active, atypical protein kinase C isoform, maintains a high level of expression in the brain after the induction of learning and long-term potentiation (LTP). Further, its overexpression enhances long-term memory and LTP. Thus, multiple lines of evidence suggest a significant role for persistently elevated PKMζ levels in long-term memory. The molecular mechanisms of how synaptic properties are regulated by the increase in PKMζ, however, are still largely unknown. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) mediates most of the fast glutamatergic synaptic transmission in the brain and is known to be critical for the expression of synaptic plasticity and memory. Importance of AMPAR trafficking has been implicated in PKMζ-mediated cellular processes, but the detailed mechanisms, particularly in terms of regulation of AMPAR lateral movement, are not well understood. In the current study, using a single-molecule live imaging technique, we report that the overexpression of PKMζ in hippocampal neurons immobilized GluA2-containing AMPARs, highlighting a potential novel mechanism by which PKMζ may regulate memory and synaptic plasticity.

Molecular brain, Jan 15, 2018

Three-dimensional (3D) reconstruction of thick samples using superresolution fluorescence microsc... more Three-dimensional (3D) reconstruction of thick samples using superresolution fluorescence microscopy remains challenging due to high level of background noise and fast photobleaching of fluorescence probes. We develop superresolution fluorescence microscopy that can reconstruct 3D structures of thick samples with both high localization accuracy and no photobleaching problem. The background noise is reduced by optically sectioning the sample using line-scan confocal microscopy, and the photobleaching problem is overcome by using the DNA-PAINT (Point Accumulation for Imaging in Nanoscale Topography). As demonstrations, we take 3D superresolution images of microtubules of a whole cell, and two-color 3D images of microtubules and mitochondria. We also present superresolution images of chemical synapse of a mouse brain section at different z-positions ranging from 0 μm to 100 μm.

Cell reports, Jan 16, 2018

Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized noc... more Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment.

Scientific reports, Jan 7, 2017

Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptiona... more Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 (SA/SA) knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in ...

Neurobiology of learning and memory, 2017

ADP-ribosylation factors (ARFs) are small guanosine triphosphatases of the Ras superfamily involv... more ADP-ribosylation factors (ARFs) are small guanosine triphosphatases of the Ras superfamily involved in membrane trafficking and regulation of the actin cytoskeleton. Aplysia Sec7 protein (ApSec7), a guanine nucleotide exchange factor for ARF1 and ARF6, induces neurite outgrowth and plays a key role in 5-hydroxyltryptamine-induced neurite growth and synaptic facilitation in Aplysia sensory-motor synapses. However, the specific role of ARF6 signaling on neurite outgrowth in Aplysia neurons has not been examined. In the present study, we cloned Aplysia ARF6 (ApARF6) and revealed that an overexpression of enhanced green fluorescent protein (EGFP)-fused constitutively active ApARF6 (ApARF6-Q67L-EGFP) could induce neurite outgrowth in Aplysia sensory neurons. Further, we observed that ApARF6-induced neurite outgrowth was inhibited by the co-expression of a Sec7 activity-deficient mutant of ApSec7 (ApSec7-E159K). The pleckstrin homology domain of ApSec7 may bind to active ApARF6 at the pla...

Molecular brain, Oct 22, 2016

Two pharmacologically distinct types of local protein synthesis are required for synapse- specifi... more Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF. ApCPEB4 which we have named after its mammalian CPEB4-like homolog lacks a prion-like domain, is responsive to 5-hydroxytryptamine, and is translated (but not transcribed) in an emetine-sensitive, rapamycin-insensitive, and PKA-dependent manner. The ApCPEB4 binds to different target RNAs than does ApCPEB. Knock-down of ApCPEB4 blocked the induction of LTF, whereas overexpression of ApCPEB4 reduces the thresh...

Proceedings of the National Academy of Sciences, 2012

The consolidation of long-term memory for sensitization and synaptic facilitation in Aplysia requ... more The consolidation of long-term memory for sensitization and synaptic facilitation in Aplysia requires synthesis of new mRNA including the immediate early gene Aplysia CCAAT enhancer-binding protein ( ApC/EBP ). After the rapid induction of ApC/EBP expression in response to repeated treatments of 5-hydroxytryptamine (5-HT), ApC/EBP mRNA is temporarily expressed in sensory neurons of sensory-to-motor synapses. However, the molecular mechanism underlying the rapid degradation of ApC/EBP transcript is not known. Here, we cloned an AU-rich element (ARE)-binding protein, ApAUF1, which functions as a destabilizing factor for ApC/EBP mRNA. ApAUF1 was found to bind to the 3′ UTR of ApC/EBP mRNA that contains AREs and subsequently reduces the expression of ApC/EBP 3′ UTR-containing reporter genes. Moreover, overexpression of ApAUF1 inhibited the induction of ApC/EBP mRNA in sensory neurons and also impaired long-term facilitation of sensory-to-motor synapses by repetitive 5-HT treatments. The...

Proceedings of the National Academy of Sciences, 2012

The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval... more The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia , and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron sy...

Science (New York, N.Y.), Jan 3, 2010

Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the cen... more Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the central nervous system, including spinal cord and cortex. Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain. We found that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKMζ in the ACC, and inhibiting PKMζ by a selective inhibitor, ζ-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKMζ in the ACC acts to maintain neuropathic pain. PKMζ could thus be a new therapeutic target for treating chronic pain.

Animal Cells and Systems, 2013

One neuron receives thousands of inputs through synapses, which contain distinct molecular compon... more One neuron receives thousands of inputs through synapses, which contain distinct molecular components and display different properties. It has been a major challenge in neuroscience to understand the development and function of specific synapses. One of the critical molecules involved in shaping synapse-specific properties is the cell adhesion molecule (CAM). Remarkable numbers of studies have shown the importance of cell-cell interaction mediated by various types of CAMs in defining synapse-specific function. Here, we summarize current understanding of CAMs playing a pivotal role in constructing neural circuits and guiding synapse-specific plasticity. Different CAMs localized at specific synapses are discussed in this review.

Scientific reports, Jan 10, 2016

Cell-permeable proteins are emerging as unconventional regulators of signal transduction and prov... more Cell-permeable proteins are emerging as unconventional regulators of signal transduction and providing a potential for therapeutic applications. However, only a few of them are identified and studied in detail. We identify a novel cell-permeable protein, mouse LLP homolog (mLLP), and uncover its roles in regulating neural development. We found that mLLP is strongly expressed in developing nervous system and that mLLP knockdown or overexpression during maturation of cultured neurons affected the neuronal growth and synaptic transmission. Interestingly, extracellular addition of mLLP protein enhanced dendritic arborization, demonstrating the non-cell-autonomous effect of mLLP. Moreover, mLLP interacts with CCCTC-binding factor (CTCF) as well as transcriptional machineries and modulates gene expression involved in neuronal growth. Together, these results illustrate the characteristics and roles of previously unknown cell-permeable protein mLLP in modulating neural development.