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Functional roles of Mst3 in radial migration during the development of mouse cerebral cortex

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Functional roles of Mst3 in radial migration during the deve...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Jacque P K ip Amy K y FU nancy y ip Division of Life Science State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience CenterThe Hong Kong University of Science and TechnologyClear Water Bay

＜正＞Objective Radial migration is critical for the lamination of cerebral cortex during early brain development. Whereas the migration of neurons requires a precise regulation of the organization and dynamics of cytoskeleton including microtubule and actin network,the underlying signaling mechanisms are not well *** the present study,we investigate the functional roles of a kinase Mst3 in radial migration during cortical *** The radial migration in mouse neocortex was investigated by in utero *** cone collapse assay in cultured hippocampal neurons was performed using confocal ***（1） We identified that Mst3, a serine/threonine kinase highly expressed in the developing mouse brain,regulates the neuronal differentiation. （2） Silencing of Mst3 by in utero electroporation resulted in a significant delay on the neuronal migration in the developing mouse neocortex.（2） Kinase activity of Mst3 was essential for its functions in neuronal morphogenesis and migration.（3） Mst3 was co-localized with F-actin at the growth cones of cultured hippocampal neurons,and regulated actin *** Kinase activity of Mst3 is important for neuronal morphogenesis and radial migration through modulation of actin dynamics.

关键词： mammalian Sterile 20-like kinase 3 Mst3 neuronal migration actin dynamics

Functional roles of melanocortin-4 receptor in hippocampal synapse

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Functional roles of melanocortin-4 receptor in hippocampal s...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Amy K.y.FU nancy y.ip Division of Life Science Molecular Neuroscience Center and State Key Laboratory of Molecular NeuroscienceThe Hong Kong University of Science and TechnologyClear Water Bay

＜正＞Objective Melanocortin-4 receptor（MC4R）,which belongs to the G-protein coupled receptor（GPCR） superfamily,is one of the five melanocortin receptors（MCRs）that is expressed abundantly in the central nervous ***4R is activated by various endogenous ligands including melanocyte stimulating hormone（MSH）,and adrenocorticotropin *** central melanocortin signaling in the hypothalamus-pituitary-adrenal axis system is critical for regulating various aspects of energy homeostasis and feeding *** MC4R is highly expressed in other brain regions such as cortex and hippocampus,the roles of MC4R in these regions remain *** this study,the functional role of MC4R in synapse plasticity in hippocampus is *** The regulation of MC4R protein in hippocampal neurons was examined using immunocytochemical analysis and Western blot *** function of MC4R in hippocampal neurons was studied by RNA interference using calcium phosphate ***（1）MC4R protein increases in rat hippocampus upon development and enriched at the synaptic compartment.（2）Knockdown of MC4R in cultured rat hippocampal neurons results in a regulation in the density of dendritic spines,the sites where excitatory synapses reside.（3）Stimulation of MC4R increases the cAMP level in hippocampal *** MC4R regulates the synapse functions through modulating the morphology of dendritic spines.

关键词： Melanocortin-4 receptor cyclic AMP dendritic spines

High-resolution two-photon transcranial imaging of brain using direct wavefront sensing

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Photonics Research 2021年第6期9卷 1144-1156页

作者： CONGPING CHEN ZHONGyA QIN SICONG HE SHAOJUN LIU SHUN-FAT LAU WANJIE WU DAN ZHU nancy y.ip JIANAN y.QU Department of Electronic and Computer Engineering The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Center of Systems Biology and Human Health The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhanChina MoE Key Laboratory for Biomedical Photonics Collaborative Innovation Center for Biomedical EngineeringSchool of Engineering SciencesHuazhong University of Science and TechnologyWuhanChina Division of Life Science The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Molecular Neuroscience Center The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina

Imaging of the brain in its native state at high spatial resolution poses major challenges to visualization ***-photon microscopy integrated with the thinned-skull or optical clearing skull technique provides a minimally invasive tool for in vivo imaging of the cortex of mice without activating immune response and inducing brain ***,the imaging contrast and spatial resolution are severely compromised by the optical heterogeneity of the skull,limiting the imaging depth to the superficial *** this work,an optimized configuration of an adaptive optics two-photon microscope system and an improved wavefront sensing algorithm are proposed for accurate correction for the aberrations induced by the skull window and brain *** this system,we achieved subcellular resolution transcranial imaging of layer 5 pyramidal neurons up to 700μm below pia in living *** addition,we investigated microglia–plaque interaction in living brain of Alzheimer’s disease and demonstrated high-precision laser dendrotomy and single-spine ablation.

关键词： resolution photon system

S-nitrosylation of Cdk5 regulates its kinase activity and dendrite growth during neuronal development

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S-nitrosylation of Cdk5 regulates its kinase activity and de...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Anthony H.K.Tsang Amy K.y.Fu Wing-yu FU Kenny K.Chung nancy y.ip Division of Life Science Molecular Neuroscience Center and State Key Laboratory of Molecular NeuroscienceThe Hong Kong University of Science and TechnologyClear Water Bay

＜正＞Objective Precise regulation of cyclin-dependent kinase 5（Cdk5）,a member of the cyclin-dependent kinase family,is critical for the proper neuronal development and ***5 is activated through its association with the neuron-specific activator p35 or ***,how its kinase activity is regulated in neurons is not well *** the present study,we investigate whether Cdk5 is regulated by the S-nitrosylation,a post-translational modification of protein,and how the S-nitrosylation of Cdk5 modulates its kinase activity and functions during neuronal *** The kinase activity of Cdk5 upon S-nitrosylation was measured using in vitro kinase *** potential physiological role of S-nitrosylation of Cdk5 in neuronal development was studied by overexpressing Cdk5 or its C83A mutant in hippocampal *** change in the neuronal morphology was examined using confocal ***（1）Cdk5 is S-nitrosylated both in vitro and in vivo.（2）S-nitrosylation of Cdk5 inhibits its kinase activity.（3）Inhibition of the S-nitrosylation of Cdk5 enhances dendrite growth in neurons. Conclusion S-nitrosylation of Cdk5 regulates its activity and dendritic development.

关键词： cyclin dependent kinase 5 p35 dendrite nitric oxide S-nitrosylation

ARMS interacts with α-syntrophin: implications for the localization and signaling of EphA4 at the neuromuscular synapse

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ARMS interacts with α-syntrophin: implications for the loca...

中国神经科学学会第六届学术会议暨学会成立十周年庆祝大会

作者： Kwok-On. Lai Juan Carlos Arévalo Stanley C. Froehner Marvin E. Adams Moses V. Chao nancy y. ip Dept. of Biochemistry Hong Kong Univ. of Science and Technology Skirball Institute of Biomolecular Medicine New york Univ. Sch. of Med. New YorkNY 10016USA Dept. of Physiology ＆ Biophysics Univ. of Washington SeattleWA 98195 USA Dept. of Physiology ＆ Biophysics Univ. of Washington SeattleWA 98195 USA Skirball Institute of Biomolecular Medicine New york Univ. Sch. of Med. New YorkNY 10016USA Dept. of Biochemistry Hong Kong Univ. of Science and Technology

＜正＞Recent accumulating evidence suggests that both Eph and Trk receptors play important roles at the neuromuscular junctions （NMJ）. The identification of ARMS （ankyrin repeat-rich membrane spanning） as a novel substrate for these receptors prompted us to investigate the potential functions of ARMS at the NMJ. In this study, we showed that ARMS was expressed in developing muscle and became concentrated at the NMJ during the first postnatal week. Using yeast two-hybrid screening, we identified the PDZ domain protein α-syntrophin as an ARMS-interacting partner in muscle. The expression profile of α-syntrophin in muscle was similar to that exhibited by ARMS and EphA4. Interestingly, overexpression of α-syntrophin induced ARMS clustering in a PDZ-dependent manner. Moreover, only α- and β2-syntrophins, but not β1 syntrophin, were able to interact with ARMS and induce the formation of ARMS clusters. In an attempt to identify other components of the ARMS/syntrophin complex, we found that ARMS associated with EphA4 and that this interaction resulted in an enhanced Jak and Stat tyrosine phosphorylation, which was further augmented by α-Syntrophin in a PDZ-dependent manner. More importantly, tyrosine phosphorylation of EphA4 induced by ephrin-A1 was attenuated in C2C12 myotubes upon the inhibition of ARMS and a-syntrophin expression by siRNA transfection. Finally, disrupted localization of ARMS and EphA4 at the NMJ was observed in a-syntrophin null mice. Taken together, our findings suggest an important role of ARMS in regulating postsynaptic signaling events through syntrophin-mediated localization of receptor tyrosine kinases.

关键词： Eph receptor receptor tyrosine kinase PDZ neuromuscular junction syntrophin

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一叶萩生物碱类成分研究

中草药 2007年第2期38卷 163-167页

作者：王英李茜叶文才叶翠芬叶玉如赵守训中国药科大学天然药物化学教研室暨南大学中药及天然药物研究所广东广州510632 香港科技大学生物化学系

目的对一叶萩的生物碱类成分进行研究。方法采用各种色谱技术对一叶萩的总生物碱部位进行分离,应用理化常数和波谱技术(NMR、MS等)鉴定化合物的结构。结果自一叶萩枝叶的总碱部位中分离得到2个新的生物碱类化合物,分别命名为叶下珠碱B(p... 详细信息

目的对一叶萩的生物碱类成分进行研究。方法采用各种色谱技术对一叶萩的总生物碱部位进行分离,应用理化常数和波谱技术(NMR、MS等)鉴定化合物的结构。结果自一叶萩枝叶的总碱部位中分离得到2个新的生物碱类化合物,分别命名为叶下珠碱B(phyllanthidine B,4α-methoxy-phyllanthidine,Ⅰ)和一叶萩醇D(securi-nolD,14β-hydroxyviroallosecurinine,Ⅱ)。结论化合物和均为新化合物。

关键词：一叶萩生物碱一叶萩型生物碱 4α-methoxy-phyllanthidine 14β-hydroxyviroallosecurinine

受体酪氨酸激酶依赖的信号转导在突触可塑性中的研究

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生命科学 2008年第5期20卷 709-711页

作者：叶玉如香港科技大学生物化学系

突触可塑性对于脑发育过程中的神经环路重构以及学习记忆等脑的高级功能是非常重要的。许多受体酪氨酸激酶家族成员,包括TrkB、ErbB和Eph在神经连接的建立和重构过程中起到核心作用。比如,突触后EphB依赖的信号会导致树突棘的产生和神... 详细信息

突触可塑性对于脑发育过程中的神经环路重构以及学习记忆等脑的高级功能是非常重要的。许多受体酪氨酸激酶家族成员,包括TrkB、ErbB和Eph在神经连接的建立和重构过程中起到核心作用。比如,突触后EphB依赖的信号会导致树突棘的产生和神经递质受体的聚集,而ephrinA引起的EphA4激活可以导致树突棘的回缩。但是,目前对EphA4依赖的树突棘重组和对神经递质受体的调节背后的机制还知之甚少。本文将集中探讨EphA4及其下游的信号通路在神经肌肉接头和中枢神经的突触中,对神经递质受体的调节功能。

关键词：突触可塑性 ephrin/EphA4信号通路细胞周期依赖激酶5

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一叶萩的化学成分

中国天然药物 2006年第4期4卷 260-263页

作者：王英李茜叶文才叶翠芬叶玉如赵守训中国药科大学天然药物化学教研室南京210009 暨南大学中药及天然药物研究所广州510632 香港科技大学生物化学系

目的:对一叶枝叶的化学成分进行研究。方法:应用各种色谱技术从一叶总碱部位中分离化合物,根据理化常数和波谱(NMR及MS等)分析方法对化合物的结构进行鉴定。结果:自一叶枝叶的总碱部位中分离得到11个化合物。分别鉴定为:(-)-15β-... 详细信息

目的:对一叶枝叶的化学成分进行研究。方法:应用各种色谱技术从一叶总碱部位中分离化合物,根据理化常数和波谱(NMR及MS等)分析方法对化合物的结构进行鉴定。结果:自一叶枝叶的总碱部位中分离得到11个化合物。分别鉴定为:(-)-15β-ethoxy-14,15-dihydroviroallosecurinine(1),一叶碱(securi-nine,2),二氢一叶碱(14,15-dihydrosecurinine,3),4-epiphyllanthine(4),securitinine(5),右旋别一叶碱(viroal-losecurinine,6),一叶醇A(securinol A,7),secu’amamine A(8),ent-phyllanthidine(9),(+)-aquilegiolide(10)和(+)-menisdaurilide(11)。结论:1为新化合物,4,8,10和11为首次从一叶中分离得到。

关键词：一叶萩生物碱 (-)-15β-ethoxy-14,15-dihydrovimallosecurinine

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老年痴呆症的分子机制

生命科学 2014年第6期26卷 550-559页

作者：沈阳陈宇傅洁瑜叶玉如香港科技大学深圳研究院广东省脑科学及疾病与药物研究重点实验室深圳518057 香港科技大学分子神经科学国家重点实验室香港科技大学生命科学部和分子神经科学中心

老年痴呆症是一种多发于老年人群的神经退行性疾病,其发病机理十分复杂,目前主要认为与β-淀粉样蛋白的神经毒性和微管结合蛋白tau的异常修饰相关。将从β-淀粉样蛋白在神经突触功能失调、神经元凋亡、炎症反应中的作用,以及tau蛋白异... 详细信息

老年痴呆症是一种多发于老年人群的神经退行性疾病,其发病机理十分复杂,目前主要认为与β-淀粉样蛋白的神经毒性和微管结合蛋白tau的异常修饰相关。将从β-淀粉样蛋白在神经突触功能失调、神经元凋亡、炎症反应中的作用,以及tau蛋白异常修饰的机理与神经损伤等方面阐述老年痴呆症发病的分子机理,并对相关诊断和治疗手段进行讨论。

关键词： β-淀粉样蛋白 tau蛋白突触损伤神经元凋亡炎症反应