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Receptor tyrosine kinases positively regulate BACE activity and Amyloid-β production through enhancing BACE internalization

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Cell research 2007年第5期17卷 389-401页

作者： Lin Zou1,2.Zhu Wang1 Li Shen1,3 Guo Bin Bao1 Tian Wang1 Jiu Hong Kang1 Gang Pei1 1 Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, shanghai institutes for biological sciences, chinese academy of sciences, {2., China 2.Clinical Molecular Medical center, Children's Hospital, Chongqing University of Medical Sicences, Chongqing 400011, China 3 Graduate School of the chinese academy of sciences, {2., China LaboratoryofMolecularCellBiology InstituteofBiochemistryandCellBiologyShanghaiInstitutesforBiologicalSciencesChineseAcademyofSciencesShanghai200031China ClinicalMolecularMedicalcenter Children'sHospitalChongqing

Amyloid-β (AP) peptide, the primary constituent of senile plaques in Alzheimer's disease (AD), is generated byβ-secretase- and γ-secretase-mediated sequential proteolysis of the amyloid precursor protein (APP). The aspartic pro-tease, β -site APP cleavage enzyme (BACE), has been identified as the main P-secretase in brain but the regulation of itsactivity is largely unclear. Here, we demonstrate that both BACE activity and subsequent Aβ production are enhancedafter stimulation of receptor tyrosine kinases (RTKs), such as the receptors for epidermal growth factor (EGF) and nervegrowth factor (NGF), in cultured cells as well as in mouse hippocampus. Furthermore, stimulation of RTKs also inducesBACE internalization into endosomes and Golgi apparatus. This enhancement of BACE activity and Aβ production uponRTK activation could be specifically inhibited by Src family kinase inhibitors and by depletion of endogenous c-Src withRNAi, and could be mimicked by over-expressed c-Src. Moreover, blockage of BACE internalization by a dominantnegative form of Rab5 also abolished the enhancement of BACE activity and Aβ production, indicating the requirementof BACE internalization for the enhanced activity. Taken together, our study presents evidence that BACE activity andAβ production are under the regulation of RTKs and this is achieved via RTK-stimulated BACE internalization, andsuggests that an aberration of such regulation might contribute to pathogenic Aβ production.

关键词： β-site APP cleavage enzyme RTK Amyloid-β Src

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Rapid Transformation of Several Elite Sweet Potato Genotypes from China

Rapid Transformation of Several Elite Sweet Potato Genotypes...

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中国植物生理学会第十次会员代表大会暨全国学术年会

作者： Jun Yang, Huiping Bi, Weijuan Fan, Min Zhang and Peng Zhang* SIBS-ETH shanghai center for Cassava {2., National Laboratory of Plant Molecular Genetics, Institute of Plant Physiology & Ecology, shanghai institutes for biological sciences, chinese academy of sciences, 300 Fenglin Road, shanghai 2.0032. China

＜正＞Efficient Agrobacterium tumefaciens-mediated transformation was developed using embryogenic suspension cultures of sweet potato [Ipomoea batatas （L.） Lam.] cultivars Ayamurasaki, Sushu2. Sushu9, Sushu11 and

关键词： sweet potato genetic transformation embryogenic suspension T-DNA

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Neuron-specific knockout of NRSF mouse is more vulnerable to the dopaminergic neurotoxin MPTP

Neuron-specific knockout of NRSF mouse is more vulnerable to...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Mei YU~(1,#),Ming LIU~(2.#),Hai-Yun SUO~1,Lei CAI~2.Jian FEI~(3,4,*) Fang HUANG~(1,*) 1 National Key Laboratory of Medical Neurobiology,shanghai Medical College,Fudan University,shanghai 2.0032. China 2.{2. of Biochemistry and Cell Biology,shanghai institutes for biological sciences,chinese academy of sciences 3 School of Life Science and Technology,Tongji Universities,shanghai 2.0092.China 4 shanghai Nan Fang Model Organism research center,shanghai 2.12.3,China

Recent studies on neuron-restrictive silencer factor(NRSF) / neuronal repressor element-1 silencing transcription factor(REST) have revealed that NRSF participates in the pathological processes of nervous system diseases,such as global ischemia,epilepsy and Huntington *** l-methyl-4-phenyI-pyridinium ion(MPP) treatment triggers the mRNA and protein expression of NRSF in human dopaminergic SH-SY5Y cells,and alteration of NRSF expression exacerbates MPP-induced cell ***,we generated a neuron-specific conditional knockout mice of NRSF(cKO) by crossing NRSF floxed mice with the neuron-specific enolase(NSE)-Cre transgenic *** or wild type mice were injected with l-methyl-4-phenyl-l,2.3,6-tetrahydropyridine(MPTP) at a dose of 15mg/kg,four times within two days,and behavioral assays were performed respectively on 1,3,7,14,2. and 2. days after the last MPTP *** were sacrificed one day after the last behavioral *** levels of DA,its metabolite 3,4-dihydroxiphenylacetic acid (DOPAC),and 5-hydroxytryptamine(5-HT) or non-relevant 5-hydroxyindoleacetic acid(5-HIAA) in striatum were analyzed by ***,the protein level of tyrosine hydroxylase(TH) in striatum was detected by Western blotting *** results showed that in the experiment of swim test,the force swimming time in both cKO and wild type mice was obviously decreased after MPTP administration,but the rate of decline in the cKO mice was higher than that in the wild type *** intoxication reduced the levels of DA,DOPAC and 5-HT in cKO and wild type mice significantly. The ratio of decrease in the cKO mice was more dramatic than that in the wild type *** the same situation happened at the level of TH in *** results suggested that neuron-specific knockout of NRSF mouse is more vulnerable to the dopaminergic neurotoxin MPTP.

关键词： NRSF MPTP conditional knockout mouse NSE promoter Parkinson’s disease

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LARGE-SCALE QUANTITATIVE PROTEOMIC research THE INTERDEPENDENCE BETWEEN CELL CYCLE AND CELL DIFFERENTIATION USING PRE-ADIPOCYTE, 3T3-L1 CELL MODEL

LARGE-SCALE QUANTITATIVE PROTEOMIC RESEARCH THE INTERDEPENDE...

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中国蛋白质组学第三届学术大会

作者： Xingjun Cao, Jianhua Zhang, Quanhu Sheng, Jie Dai, Jiarui Wu, Rong Zeng research center for Proteome Analysis, Key Lab of Proteomics, Institute of Biochemistry and Cell Biology, {2., chinese academy of sciences, shanghai, 2.0031, China

Pre-adipocyte 3T3-L1 cell is a kind of excellent models to study the cell differentiation. It is required about two days for the cells from the confluence to the status that enter into the GO phase and could be induced by the inducers to cell differentiation during the cell culture. In this process the mechanism how the cells retreat from the cell cycle gradually is yet unknown. Here we applied a novel quantitative proteomic strategy, SILAC

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Wrinkled petals and stamens 1,is required for the morphogenesis of petals and stamens in Lotus japonicus

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Cell research 2006年第5期16卷 499-506页

作者： Jiang Hua Chen~1 Ji Liang Pang~2.Li Lin Wang~2.Yong Hai Luo~1 Xin Li~3 Xiang Ling Cao~1 Kui Lin~3 Wei Ma~3 Xiao He Hu~1 Da Luo~(1,3) ~1National Laboratory of Plant Molecular Genetics,Institute of Plant Physiology and Ecology,shanghai institutes for biological sciences,and Graduate School of the chinese academy of sciences,chinese academy of sciences,300 Fenglin Road,shanghai 2.0032.China ~2.chool of Life Science,Hangzhou Normal College,16 Xuelin Road,Hangzhou 310018,China ~3School of Life Science and biotechnology,shanghai Jiao Tong University,1954 Huashan Road,shanghai 2.0030,China NationalLaboratoryofPlantMolecularGenetics InstituteofPlantPhysiologyandEcologyShanghaiInstitutesforBiologicalSciencesandGraduateSchooloftheChineseAcademyofSciencesChineseAcademyofSciences300FenglinRoad

Although much progress has been made in understanding how floral organ identity is determined during the floraldevelopment,less is known about how floral organ is elaborated in the late floral developmental *** we de-scribe a novel floral mutant,wrinkledt petals and stamensl (wps1),which shows defects in the development of petalsand *** analysis indicates that wps1 mutant is corresponding to a single recessive locus at the long arm ofchromosome *** early development of floral organs in wps1 mutant is similar to that in wild type,and the malfunctionof the mutant commences in late developmental stages,displaying a defect on the appearance of petals and *** mature flower,petals and stamen filaments in the mutant are wrinkled or folded,and the cellular morphology underL1 layer of petals and stamen filaments is *** is found that the expression patterns of floral organ identity genesare not affected in wps1 mutants compared with that of wild type,consistent with the unaltered development of allfloral ***,the identities of epidermal cells in different type of petals are *** histologicalanalysis shows that in wps1 flowers all petals are irregularly folded,and there are knotted structures in the petals,whilethe shape and arrangement of inner cells are malformed and *** on these results,we propose that Wps1acts downstream to the class B floral organ identity genes,and functions to modulate the cellular differentiation duringthe late flower developmental stages.

关键词： Lotus japonicus wps1 mutant ABC model floral organ differentiation

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Slit-2.repels the migration of olfactory ensheathing cells by triggering Ca2.-dependent cofilin activation and RhoA inhibition

Slit-2 repels the migration of olfactory ensheathing cells b...

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中国生理学会第2.届全国会员代表大会暨生理学学术大会

作者： Zhi-Hui HUANG~(1,2.,Ying WANG~(1,2.,Zhi-Da SU~2.Jian-Guo GENG~4,Yi-Zhang CHEN~2.Xiao-Bing YUAN~(3,*), Cheng HE~(2.*) 1 School of Basic Medicine Science,Wenzhou Medical College,Wenzhou,Zhejiang 32.035 2.Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education,Neuroscience research center of Changzheng Hospital,Second Military Medical University,{2. 2.0433 3 Institute of Neuroscience and State Key Laboratory of Neuroscience,chinese academy of sciences, shanghai 2.0031 4 Institute of Biochemistry and Cell Biology,shanghai institutes for biological sciences,chinese academy of sciences, shanghai 2.0031

Olfactory ensheathing cells(OECs) migrate from the olfactory epithelium towards the olfactory bulb during ***,the guidance mechanism for OEC migration remains a *** we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2.A gradient of Slit-2.in front of cultured OECs first caused the collapse of the leading front,then the reversal of cell *** Slit-2.effects depended on the Ca release from internal stores through IP3 receptor ***,in response to Slit-2.stimulation,collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca- dependent manner,whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the ***,the Slit-2.induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA *** findings revealed Slit-2.as a repulsive guidance factor for OEC migration and an unexpected link between Ca and cofilin signaling during Slit-2.triggered repulsion.

关键词： olfactory ensheathing cells Slit-2 migration cofilin calcium RhoA

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Experience-dependent visual feature extracting in Drosophila

Experience-dependent visual feature extracting in Drosophila

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The Third Asian Conference on Vision (ACV2.04)

作者： Yueqing Peng Wei Zhang & Aike Guo Institute of Neuroscience shanghai institutes for biological sciences chinese academy of sciences 32. Yue-yang Road {2. China. Laboratory of Visual Information Processing center for Brain and Cognitive sciences Institute of Biophysics chinese academy of sciences 15 Da-tun Road Chao-yang Dist. Beijing 100101 China

＜正＞ Visual feature extracting is defined as selecting main component from multiple visual features, such as color, shape, and so on. Certain kind of higher level cognitive processing is required to complete this task. The fruit flies are able to learn both color and shape cues. But we don’t know whether such a tiny brain can extract the most important cue in the case of complex feature combination. On the other hand, many cognitive processes can be modulated by

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The role of water channel proteins and nitric oxide signaling in rice seed germination

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Cell research 2007年第7期17卷 638-649页

作者： Sang-Soo Kwak Korea research Institute of Bioscience and biotechnology Oun-dong 52.Yusong Taejon 305-333 South Korea

Previous studies have demonstrated the possible role of several aquaporins in seed germination. But systematic inves-tigation of the role of aquaporin family members in this process is lacking. Here, the developmental regulation of plasmamembrane intrinsic protein (PIP) expression throughout germination and post-germination processes in rice embryoswas analyzed. The expression patterns of the PIPs suggest these aquaporins play different roles in seed germination andseedling growth. Partial silencing of the water channel genes, OsPIP1;1 and OsPIP1;3, reduced seed germination whileover-expression of OsPIP1;3 promoted seed germination under water-stress conditions. Moreover, spatial expressionanalysis indicates that OsPIP1;3 is expressed predominantly in embryo during seed germination. Our data also revealedthat the nitric oxide (NO) donors, sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO), promoted seed germi-nation; furthermore, the NO scavenger, 2.(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, inhibitedgermination and reduced the stimulative effects of SNP and GSNO on rice germination. Exogenous NO stimulated thetranscription of OsPIP1;1, OsPIP1;2. OsPIP1;3 and OsPIP2.8 in germinating seeds. These results suggest that waterchannels play an important role in seed germination, acting, at least partly, in response to the NO signaling pathway.

关键词： germination nitric oxide Oryza sativa over-expression silencing water channel

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Monitoring dynamic protein-protein interactions during GABA,receptor mediated IGF-IR transactivation by an activity based probe

Monitoring dynamic protein-protein interactions during GABA,...

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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： Fa-Jun NAN~2.Jian-Feng LIU~1 1 Sino-France Laboratory for Drug Screening,Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan,China 2.National center for Drug Screening,State Key Laboratory of Drug research,{2. Institute of MateriaMedica, {2. institutes of biological sciences,chinese academy of sciences,{2.,China

Many GPCR agonists can activate receptor-tyrosine-kinases(RTKs) through transactivation,the mechanisms of which are poorly ***,we have investigated IGF-1 receptor(IGF-IR) transactivation by GABA receptor using a chemical biology approach in rat primary *** show that GABA receptor activation induces a dynamic assembly and disassembly of a protein complex,including both receptors and their downstream ***,a non-receptor tyrosine kinase,plays a key role in coordinating this dynamic ***,such a dynamic process is critical for transactivation and transactivation-dependent neuronal *** results reveal an important mechanism underlying GPCR transactivation of RTKs.

关键词： GABAB receptor IGF-IR transactivation FAK dynamic protein-protein interactions activity-based probe

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Human embryonic stem cell lines derived from the chinese population

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Cell research 2005年第5期15卷 394-400页

作者： Zhen Fu FANG1,2. Fan JIN3, Hui GAI1, Ying CHEN1, Li WU1, Ai Lian LIU1, Bin CHEN1, Hui Zhen SHENG1,2.* 1center for Developmental Biology, Xinhua Hospital, shanghai Second Medical University, 1665 Kong Jiang Road, Shang- hai 2.0092. China 2.aboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, {2., chinese academy of sciences, shanghai 2.0031, China 3In vitro Fertilization center of Women’s Hospital, School of Medicine, Zhejiang University, Zhejiang 310006, China centerforDevelopmentalBiology XinhuaHospitalShanghaiSecondMedicalUniversity1665KongJiangRoadShanghai200092

Six human embryonic stem cell lines were established from surplus blastocysts. The cell lines expressed alkaline phosphatase and molecules typical of primate embryonic stem cells, including Oct-4, Nanog, TDGF1, Sox2. EBAF, Thy-1, FGF4, Rex-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. Five of the six lines formed embryoid bodies that expressed markers of a variety of cell types; four of them formed teratomas with tissue types representative of all three embryonic germ layers. These human embryonic stem cells are capable of producing clones of undifferentiated morphology, and one of them was propagated to become a subline. Human embryonic stem cell lines from the chinese population should facilitate stem cell research and may be valuable in studies of population genetics and ecology.

关键词： human embryonic stem cell pluoripotent cell line teratoma.

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