Seungnam Han

Korea Advanced Institute of Science and Technology

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Eunjoon Kim

Korea Advanced Institute of Science and Technology

Se‐Young Choi

Seoul National University

Karam Kim

University of California, Davis

Jinsoo Seo

Massachusetts Institute of Technology

Kihoon Han

Korea University

Jeonghoon Choi

Gwangju Institute of Science and Technology

Yong Chul Bae

Kyungpook National University

Hyun Kim

Korea University

Myoung‐Hwan Kim

Seoul National University Bundang Hospital

Jinhee Yang

Seoul National University

Cooperative Institutions

Korea Advanced Institute of Science and Technology

Seoul National University

Howard Hughes Medical Institute

Institute for Basic Science

Korea University

Kyungpook National University

Daegu Gyeongbuk Institute of Science and Technology

Yonsei University

Johns Hopkins University

Massachusetts Institute of Technology

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD

Kihoon Han Myoung‐Hwan Kim Daniel P. Seeburg Jinsoo Seo Chiara Verpelli

Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)–dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear. We show here that a regulated interaction of the endocytic adaptor RalBP1 with two synaptic proteins, the small GTPase RalA and the postsynaptic scaffolding protein PSD-95, controls NMDAR-dependent AMPAR endocytosis during LTD. NMDAR activation stimulates RalA, which binds and translocates widespread RalBP1 to synapses. In addition, NMDAR activation dephosphorylates RalBP1, promoting the interaction of RalBP1 with PSD-95. These two regulated interactions are required for NMDAR-dependent AMPAR endocytosis and LTD and are sufficient to induce AMPAR endocytosis in the absence of NMDAR activation. RalA in the basal state, however, maintains surface AMPARs. We propose that NMDAR activation brings RalBP1 close to PSD-95 to promote the interaction of RalBP1-associated endocytic proteins with PSD-95-associated AMPARs. This suggests that scaffolding proteins at specialized cellular junctions can switch their function from maintenance to endocytosis of interacting membrane proteins in a regulated manner.

Source

Cite

Citations (0)

Regulation of hippocampal long‐term potentiation and long‐term depression by diacylglycerol kinaseζ

Hippocampus (2010)

Jinsoo Seo Karam Kim Seil Jang Seungnam Han Se‐Young Choi

Abstract Diacylglycerol (DAG) is an important signaling molecule at neuronal synapses. Generation of synaptic DAG is triggered by the activation of diverse surface receptors including N ‐methyl‐ D ‐aspartate (NMDA) receptors and metabotropic glutamate receptors. The action of DAG is terminated by enzymatic conversion of DAG to phosphatidic acid (PA) by DAG kinases (DGKs). DGKζ, one of many mammalian DGKs, is localized to synapses through direct interaction with the postsynaptic scaffolding protein PSD‐95, and regulates dendritic spine maintenance by promoting DAG‐to‐PA conversion. However, a role for DGKζ in the regulation of synaptic plasticity has not been explored. We report here that Schaffer collateral‐CA1 pyramidal synapses in the hippocampus of DGKζ‐knockout (DGKζ −/− ) mice show enhanced long‐term potentiation (LTP) and attenuated long‐term depression (LTD). The attenuated LTD at DGKζ −/− synapses involves both NMDA receptors and metabotropic glutamate receptors. These changes in LTP and LTD were reversed by phospholipase C inhibition, which blocks DAG production. Similar reversals in both LTP and LTD were also induced by inhibition of protein kinase C, which acts downstream of DAG. These results suggest that DGKζ regulates hippocampal LTP and LTD by promoting DAG‐to‐PA conversion, and establish that phospholipase C and protein kinase C lie upstream and downstream, respectively, of DGKζ‐dependent regulation of hippocampal LTP and LTD. © 2010 Wiley Periodicals, Inc.

Long-term depression

Schaffer collateral

10.1002/hipo.20889

Cite

Citations (32)

Regulation of Dendritic Spines, Spatial Memory, and Embryonic Development by the TANC Family of PSD-95-Interacting Proteins

Journal of Neuroscience (2010)

Seungnam Han Jungyong Nam Yan Li Se-Ho Kim Suk-Hee Cho

PSD-95 (postsynaptic density-95) is thought to play important roles in the regulation of dendritic spines and excitatory synapses, but the underlying mechanisms have not been fully elucidated. TANC1 is a PSD-95-interacting synaptic protein that contains multiple domains for protein-protein interactions but whose function is not well understood. In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. Overexpression of TANC1 and TANC2 in cultured neurons increases the density of dendritic spines and excitatory synapses in a manner that requires the PDZ (PSD-95/Dlg/ZO-1)-binding C termini of TANC proteins. TANC1-deficient mice exhibit reduced spine density in the CA3 region of the hippocampus, but not in the CA1 or dentate gyrus regions, and show impaired spatial memory. TANC2 deficiency, however, causes embryonic lethality. These results suggest that TANC1 is important for dendritic spine maintenance and spatial memory, and implicate TANC2 in embryonic development.

Postsynaptic density

PDZ domain

Dendritic filopodia

10.1523/jneurosci.3128-10.2010

Cite

Citations (68)

Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD

PLoS Biology (2009)

Kihoon Han Myoung‐Hwan Kim Daniel P. Seeburg Jinsoo Seo Chiara Verpelli

10.1371/journal.pbio.1000187

Cite

Citations (68)

PSD-95 interacts with RalBP1.

Han Kihoon Kim Myoung-Hwan Seeburg Daniel Seo Jinsoo Chiara Verpelli

10.1371/journal.pbio.1000187.g001

Cite

Citations (0)

Enhanced NMDA Receptor-Mediated Synaptic Transmission, Enhanced Long-Term Potentiation, and Impaired Learning and Memory in Mice Lacking IRSp53

Journal of Neuroscience (2009)

Myoung‐Hwan Kim Jeonghoon Choi Jinhee Yang Woosuk Chung Ji‐Hyun Kim

IRSp53 is an adaptor protein that acts downstream of Rac and Cdc42 small GTPases and is implicated in the regulation of membrane deformation and actin filament assembly. In neurons, IRSp53 is an abundant postsynaptic protein and regulates actin-rich dendritic spines; however, its in vivo functions have not been explored. We characterized transgenic mice deficient of IRSp53 expression. Unexpectedly, IRSp53(-/-) neurons do not show significant changes in the density and ultrastructural morphologies of dendritic spines. Instead, IRSp53(-/-) neurons exhibit reduced AMPA/NMDA ratio of excitatory synaptic transmission and a selective increase in NMDA but not AMPA receptor-mediated transmission. IRSp53(-/-) hippocampal slices show a markedly enhanced long-term potentiation (LTP) with no changes in long-term depression. LTP-inducing theta burst stimulation enhances NMDA receptor-mediated transmission. Spatial learning and novel object recognition are impaired in IRSp53(-/-) mice. These results suggest that IRSp53 is involved in the regulation of NMDA receptor-mediated excitatory synaptic transmission, LTP, and learning and memory behaviors.

Long-term depression

Postsynaptic density

10.1523/jneurosci.4306-08.2009

Cite

Citations (137)

Synaptic removal of diacylglycerol by DGKζ and PSD-95 regulates dendritic spine maintenance

The EMBO Journal (2009)

Karam Kim Jinhee Yang Xiao-Ping Zhong Myoung‐Hwan Kim Yun‐Sook Kim

Postsynaptic density

Retrograde signaling

10.1038/emboj.2009.44

Cite

Citations (63)

Regulation of Synaptic Rac1 Activity, Long-Term Potentiation Maintenance, and Learning and Memory by BCR and ABR Rac GTPase-Activating Proteins

Journal of Neuroscience (2010)

Daeyoung Oh Seungnam Han Jinsoo Seo Jae-Ran Lee Jeonghoon Choi

Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer's disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-positive chronic myelogenous leukemia. Despite the fact that BCR mRNAs are abundantly expressed in the brain, the neural functions of BCR protein have remained obscure. We report here that BCR and its close relative active BCR-related (ABR) localize at excitatory synapses and directly interact with PSD-95, an abundant postsynaptic scaffolding protein. Mice deficient for BCR or ABR show enhanced basal Rac1 activity but only a small increase in spine density. Importantly, mice lacking BCR or ABR exhibit a marked decrease in the maintenance, but not induction, of long-term potentiation, and show impaired spatial and object recognition memory. These results suggest that BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions.

10.1523/jneurosci.1711-10.2010

Cite

Citations (107)

DGKι regulates presynaptic release during mGluR-dependent LTD

The EMBO Journal (2010)

Jinhee Yang Jinsoo Seo Ramya Nair Seungnam Han Seil Jang

10.1038/emboj.2010.286

Cite

Citations (51)