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Daegu, South Korea

Kim Y.,Seoul National University | Ha C.M.,Seoul National University | Ha C.M.,Korea Brain Research Institute | Chang S.,Seoul National University
Journal of Biological Chemistry | Year: 2013

SNX26, a brain-enriched RhoGAP, plays a key role in dendritic arborization during early neuronal development in the neocortex. In mature neurons, it is localized to dendritic spines, but little is known about its role in later stages of development. Our results show that SNX26 interacts with PSD-95 in dendritic spines of cultured hippocampal neurons, and as a GTPase-activating protein for Cdc42, it decreased the F-actin content in COS-7 cells and in dendritic spines of neurons. Overexpression of SNX26 resulted in a GTPase-activating protein activity-dependent decrease in total protrusions and spine density together with dramatic inhibition of filopodia-to-spine transformations. Such effects of SNX26 were largely rescued by a constitutively active mutant of Cdc42. Consistently, an shRNA-mediated knockdown of SNX26 significantly increased total protrusions and spine density, resulting in an increase in thin or stubby type spines at the expense of the mushroom spine type. Moreover, endogenous expression of SNX26 was shown to be bi-directionally modulated by neuronal activity. Therefore, we propose that in addition to its key role in neuronal development, SNX26 also has a role in the activity-dependent structural change of dendritic spines in mature neurons. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Source

Greene M.J.,Massachusetts Institute of Technology | Kim J.S.,Princeton University | Kim J.S.,Korea Brain Research Institute | Seung H.S.,Princeton University
Cell Reports | Year: 2016

Visual motion information is computed by parallel On and Off pathways in the retina, which lead to On and Off types of starburst amacrine cells (SACs). The approximate mirror symmetry between this pair of cell types suggests that On and Off pathways might compute motion using analogous mechanisms. To test this idea, we reconstructed On SACs and On bipolar cells (BCs) from serial electron microscopic images of a mouse retina. We defined a new On BC type in the course of classifying On BCs. Through quantitative contact analysis, we found evidence that sustained and transient On BC types are wired to On SAC dendrites at different distances from the SAC soma, mirroring our previous wiring diagram for the Off BC-SAC circuit. Our finding is consistent with the hypothesis that On and Off pathways contain parallel correlation-type motion detectors. © 2016 The Authors. Source

Lim H.-H.,Brandeis University | Lim H.-H.,Howard Hughes Medical Institute | Lim H.-H.,Korea Brain Research Institute | Stockbridge R.B.,Brandeis University | And 3 more authors.
Nature Chemical Biology | Year: 2013

Cl - /H + antiporters of the CLC superfamily transport anions across biological membranes in varied physiological contexts. These proteins are weakly selective among anions commonly studied, including Cl -, Br -, I -, NO 3 - and SCN -, but they seem to be very selective against F -. The recent discovery of a new CLC clade of F - /H + antiporters, which are highly selective for F - over Cl -, led us to investigate the mechanism of Cl - -over-F - selectivity by a CLC Cl - /H + antiporter, CLC-ec1. By subjecting purified CLC-ec1 to anion transport measurements, electrophysiological recording, equilibrium ligand-binding studies and X-ray crystallography, we show that F - binds in the Cl - transport pathway with affinity similar to Cl - but stalls the transport cycle. Examination of various mutant antiporters implies a 'lock-down' mechanism of F - inhibition, in which F -, by virtue of its unique hydrogen-bonding chemistry, greatly retards a proton-linked conformational change essential for the transport cycle of CLC-ec1. © 2013 Nature America, Inc. All rights reserved. Source

Jha M.K.,Kyungpook National University | Lee S.,Kyungpook National University | Lee S.,Korea Brain Research Institute | Park D.H.,Kyungpook National University | And 4 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2015

Lipocalin-2 (LCN2) is an acute phase protein with multiple functions that has garnered a great deal of interest over the last decade. However, its precise role in the pathophysiology of the central nervous system (CNS) remains to be outlined. Emerging evidence indicates that LCN2 is synthesized and secreted as an inducible factor from activated microglia, reactive astrocytes, neurons, and endothelial cells in response to inflammatory, infectious, or injurious insults. More recently, it has been recognized as a modulatory factor for diverse cellular phenotypes in the CNS, such as cell death, survival, morphology, migration, invasion, differentiation, and functional polarization. LCN2 induces chemokine production in the CNS in response to inflammatory challenges, and actively participates in the innate immune response, cellular influx of iron, and regulation of neuroinflammation and neurodegeneration. LCN2 also modulates several biobehavioral responses including pain hypersensitivity, cognitive functions, emotional behaviors, depression, neuronal excitability, and anxiety. This review covers recent advances in our knowledge regarding functional roles of LCN2 in the CNS, and discusses how LCN2 acts as an autocrine mediator of astrocytosis, a chemokine inducer, and a modulator of various cellular phenotypes in the CNS. We finally explore the possibilities and challenges of employing LCN2 as a signature of several CNS anomalies. © 2014 Elsevier Ltd. Source

Choi Y.P.,National Institute of Allergy and Infectious Diseases | Choi Y.P.,Korea Brain Research Institute | Head M.W.,University of Edinburgh | Ironside J.W.,University of Edinburgh | Priola S.A.,National Institute of Allergy and Infectious Diseases
American Journal of Pathology | Year: 2014

Sporadic Creutzfeldt-Jakob disease is the most common of the human prion diseases, a group of rare, transmissible, and fatal neurologic diseases associated with the accumulation of an abnormal form (PrPSc) of the host prion protein. In sporadic Creutzfeldt-Jakob disease, disease-associated PrPSc is present not only as an aggregated, protease-resistant form but also as an aggregated protease-sensitive form (sPrPSc). Although evidence suggests that sPrPSc may play a role in prion pathogenesis, little is known about how it interacts with cells during prion infection. Here, we show that protease-sensitive abnormal PrP aggregates derived from patients with sporadic Creutzfeldt-Jakob disease are taken up and degraded by immortalized human astrocytes similarly to abnormal PrP aggregates that are resistant to proteases. Our data suggest that relative proteinase K resistance does not significantly influence the astrocyte's ability to degrade PrPSc. Furthermore, the cell does not appear to distinguish between sPrPSc and protease-resistant PrPSc, suggesting that sPrPSc could contribute to prion infection. © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. Source

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