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

Han, Kihoon,Kim, Myoung-Hwan,Seeburg, Daniel,Seo, Jinsoo,Verpelli, Chiara,Han, Seungnam,Chung, Hye Sun,Ko, Jaewon,Lee, Hyun Woo,Kim, Karam,Heo, Won Do,Meyer, Tobias,Kim, Hyun,Sala, Carlo,Choi, Se-Youn Public Library of Science 2009 PLoS biology Vol.7 No.9

<▼1><P>A two step mechanism was identified that regulates receptor endocytosis during the development of long-term depression (LTD), a long-lasting decrease in synaptic transmission.</P></▼1><▼2><P>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.</P></▼2><▼3><P><B>Author Summary</B></P><P>Neurons adapt over time in order to dampen their response to prolonged or particularly strong stimuli. This process, termed long-term depression (LTD), results in a long-lasting decrease in the efficiency of synaptic transmission. One extensively studied form of LTD requires the activation of a specific class of receptors known as NMDA glutamate receptors (NMDARs). A key molecular event initiated by NMDA receptor activation is the stimulation of protein phosphatases. Another key event is internalization via endocytosis of synaptic AMPA glutamate receptors (AMPARs). However, the mechanism by which protein dephosphorylation is coupled to AMPAR endocytosis has remained unclear. Here, we help to define this mechanism. We show that endocytic proteins, including RalBP1, are widely distributed in neurons under normal conditions. Upon NMDAR activation, the small GTPase RalA becomes activated and binds to RalBP1, resulting in the translocation of RalBP1 and RalBP1-associated endocytic proteins to synapses. At the same time, RalBP1 becomes dephosphorylated, which promotes its binding to the postsynaptic scaffold protein PSD-95, a protein that itself associates with AMPARs. This concerted recruitment of endocytic proteins to the vicinity of AMPARs results in AMPAR endocytosis. On the basis of our data, we propose a model in which dual binding of RalBP1 to both RalA and PSD-95 following RalBP1 dephosphorylation is essential for NMDAR-dependent AMPAR endocytosis during LTD.</P></▼3>

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

Han, Seungnam,Nam, Jungyong,Li, Yan,Kim, Seho,Cho, Suk-Hee,Cho, Yi Sul,Choi, So-Yeon,Choi, Jeonghoon,Han, Kihoon,Kim, Youngrim,Na, Moonseok,Kim, Hyun,Bae, Yong Chul,Choi, Se-Young,Kim, Eunjoon The Society 2010 The Journal of neuroscience Vol.30 No.45

<P>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.</P>

Fragile X-like behaviors and abnormal cortical dendritic spines in <i>Cytoplasmic FMR1-interacting protein 2</i>-mutant mice

Han, Kihoon,Chen, Hogmei,Gennarino, Vincenzo A.,Richman, Ronald,Lu, Hui-Chen,Zoghbi, Huda Y. IRL Press 2015 Human molecular genetics Vol.24 No.7

<P>Silencing of fragile X mental retardation 1 (<I>FMR1</I>) gene and loss of fragile X mental retardation protein (FMRP) cause fragile X syndrome (FXS), a genetic disorder characterized by intellectual disability and autistic behaviors. FMRP is an mRNA-binding protein regulating neuronal translation of target mRNAs. Abnormalities in actin-rich dendritic spines are major neuronal features in FXS, but the molecular mechanism and identity of FMRP targets mediating this phenotype remain largely unknown. Cytoplasmic FMR1-interacting protein 2 (Cyfip2) was identified as an interactor of FMRP, and its mRNA is a highly ranked FMRP target in mouse brain. Importantly, Cyfip2 is a component of WAVE regulatory complex, a key regulator of actin cytoskeleton, suggesting that Cyfip2 could be implicated in the dendritic spine phenotype of FXS. Here, we generated and characterized <I>Cyfip2</I>-mutant (<I>Cyfip2<SUP>+/−</SUP></I>) mice. We found that <I>Cyfip2<SUP>+/−</SUP></I> mice exhibited behavioral phenotypes similar to <I>Fmr1</I>-null (<I>Fmr1<SUP>−/y</SUP></I>) mice, an animal model of FXS. Synaptic plasticity and dendritic spines were normal in <I>Cyfip2<SUP>+/−</SUP></I> hippocampus. However, dendritic spines were altered in <I>Cyfip2<SUP>+/−</SUP></I> cortex, and the dendritic spine phenotype of <I>Fmr1<SUP>−/y</SUP></I> cortex was aggravated in <I>Fmr1<SUP>−/y</SUP></I>; <I>Cyfip2<SUP>+/−</SUP></I> double-mutant mice. In addition to the spine changes at basal state, metabotropic glutamate receptor (mGluR)-induced dendritic spine regulation was impaired in both <I>Fmr1<SUP>−/y</SUP></I> and <I>Cyfip2<SUP>+/−</SUP></I> cortical neurons. Mechanistically, mGluR activation induced mRNA translation-dependent increase of Cyfip2 in wild-type cortical neurons, but not in <I>Fmr1<SUP>−/y</SUP></I> or <I>Cyfip2<SUP>+/−</SUP></I> neurons. These results suggest that misregulation of Cyfip2 function and its mGluR-induced expression contribute to the neurobehavioral phenotypes of FXS.</P>

가슴압박소생술 시 교육수준에 따른 지면반력 및 압력중심의 차이

( Kihoon Han ),( Ho-jong Gil ),( Mi-kyoung Lee ),( Joonsung Park ),( Jongbin Kim ) 한국운동역학회 2021 한국운동역학회지 Vol.31 No.3

Objective: The purpose of this study was to investigate the effect of levels of education on ground reaction force and center of pressure parameters during chest compression resuscitation. Method: Twenty male university students were divided into two groups; certified group (CG, n=10) and non-certified group (NCG, n=10). Two force plates were used to measure ground reaction force and center of pressure parameters during 30 times (three trials) chest compression resuscitation. Independent t-tests were used to compare ground reaction force and center of pressure parameters between two groups. An alpha level of 0.05 was used in all tests. Results: All chest-compression time parameters (total time, 1 systolic time, and diastolic time) in CG were significantly shorter than those in NCG (p<.05). Fy of the diastolic and Fz of the systolic in CG revealed significantly the larger GRF values and Fy of the systolic in CG showed significantly the smaller GRF value (p<.05). The standard deviation of Fz of the systolic and diastolic within the subject during 30 times chestcompression resuscitation revealed significantly the smaller values in CG (p<.05). Conclusion: First, CG performed chest compressions efficiently at an appropriate rate compared to NCG. Second, CG showed lower Fx and Fy values in both the mediolateral and anteroposterior axes compared to NCG, which reduced unnecessary chest-compression force consumption and minimized the movement in patients with cardiac arrest. Third, CG showed high Fz value of the systolic and low Fz value of the diastolic. Based on this, chest compression resuscitation was performed to increase the survival rate of cardiac arrest patients.

Behavior Based Decentralized Controller Design For Unmanned Aerial Vehicle Swarm

Kihoon Han,Jieun Lee,Youdan Kim 한국항공우주학회 2008 한국항공우주학회 학술발표회 논문집 Vol.- No.-

This paper deals with a behavior based decentralized control strategy for unmanned aerial vehicle (UAV) swarming. Individual interactions for swarming behavior are modeled using the artificial potential functions. For tracking the reference trajectory of UAV swarming, a swarming center is considered as the object of control. The sliding-mode control technique is used to make the proposed swarm control strategy robust with respect to the system uncertainties. Collision avoidance against obstacles and pop-up threats is also considered. Numerical simulations are performed to verify the performance of the proposed controller.

다운증후군 아동의 발목 근력과 유연성 향상 운동프로그램 참여가 보행 패턴 및 균형능력에 미치는 영향

한기훈 ( Kihoon Han ),김종빈 ( Jong-bin Kim ),윤석민 ( Seok-min Yun ) 한국특수체육학회 2021 한국특수체육학회지 Vol.29 No.3

본 연구는 발목 움직임을 발생시키는 근육들의 근력, 유연성 향상을 위한 운동 프로그램 참여가 다운 증후군 아동들의 보행능력과 균형능력에 어떠한 영향을 줄 수 있을지 과학적으로 검증해 보는데 그 목적이 있다. 연구대상은 B광역시에 거주하는 10명의 다운증후군 아동들이 참여하였다. 운동 프로그램 참여 전·후 발뒤꿈치 접지시간 비율, 보행각도, 발의 회내 비율, 양발서기와 오른발/왼발 외발서기 시 균형능력을 대응표본 t-검정(paired t-test)을 실시하여 측정 변인 간에 사전/사후 결과 차이를 검증 하였다. 그 결과 첫째, 발뒤꿈치가 접촉 시간이 증가되어 발이 흡수하는 충격을 분산 시키는 효과가 있었다. 둘째, 양발보행각도의 감소로 인해 정상인의 보행각도에 근접한 결과를 보여주었다. 셋째, 양발지지와 오른발/왼발지지 조건 모두에서 균형능력의 향상을 보였다. The purpose of this study is to scientifically verify how participation in an ankle muscle strength and flexibility training can affect to improve the gait pattern and balance ability of children with Down syndrome. The participants for this study were 10 children with Down's syndrome living in metropolitan city B. The heel contact time ratio, gait angle, more pronated change ratio, and balance ability when standing on both feet and right/left uni-foot standing before and after participating in ankle muscle strength and flexibility training were measured and conducted to a paired t-test to compare the results between pre and post test. As a result, first, the heel contact time ratio was increased, which has the effect of dispersing the shock absorbed by the foot. Second, the gait angle was close to that of a normal person. Third, balance abilities were improved in both foot support and right/left foot support conditions.

차량 모션 피드백 ECS 제어

길한별(Han-Byeol Gil),최기훈(Kihoon Choi),안성제(Seong-Je An),정성희(Sung-Hee Jung),조완기(Wanki Cho),유승한(Seung-Han You) 한국자동차공학회 2023 한국자동차공학회 학술대회 및 전시회 Vol.2023 No.11

Test Pulse를 이용한 DCT 제어용 BLDC Motor Hall 센서 진단 개선

한기훈(Kihoon Han),신황철(Hwangchul Shin),김태훈(Taehoon Kim) 한국자동차공학회 2014 한국자동차공학회 학술대회 및 전시회 Vol.2014 No.11

DCT 제어기 설계 및 검증을 위한 HIL 기반의 시험 자동화 시스템 구축

한기훈(Kihoon Han),주희훈(Heehun Ju) 한국자동차공학회 2011 한국자동차공학회 부문종합 학술대회 Vol.2011 No.5

DCT system is innovational transmission system. But because of complexity of DCT system, model based development is essential for DCT TCU function development. Also, new validation system is necessary to reduce development / validation cycle time and cost. This study suggests the a HIL(Hardware-In-the-Loop) simulator, which can validate DCT TCU system, and HIL based automated test process. This system can not only reduce the development/validation cycle time and cost but also ensure more reliable vehicle quality. This automated test process makes possible to perform tests that require critical timing, hazardous environment, complex scenario and repetitive practice under various conditions. And we can obtain more reliable test results, as well as validation cycle time is reduced and the quality of vehicle is improved.

노면 경사도 추정 기법을 이용한 CVT 최적 정속 주행 제어 기법에 관한 연구

한기훈(Kihoon Han),이동진(Dongjin Lee) 한국자동차공학회 2010 한국자동차공학회 학술대회 및 전시회 Vol.2010 No.11

Estimation of longitudinal load such as road slope and rolling resistance is essential for precise cruise control of automotives. In this paper, using model based road slope estimation method with gravity sensor, precise longitudinal dynamic model of automotive vehicle is presented for vehicle auto-cruise control. Continuously Variable Transmissions (CVT) can cover a wide range of ratios and shift the engine operating points for a certain demanded power towards higher loads and lower speeds. This makes it possible to operate a combustion engine in more efficient working points than stepped. With this merit, fuel optimal cruise control by CVT ratio control is possible using precise longitudinal dynamic model using model based road slope estimation.