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| 1 | 与神经退行性疾病相关的RNA结合蛋白在线粒体损伤中的作用显示文摘线粒体是细胞内制造能量的细胞器,它还负责各种细胞信号的整合,参与协调多种复杂的细胞功能.线粒体是动态变化的,连续不断地进行分裂与融合,这是其功能维持和增殖遗传的关键.在过去20年中,参与线粒体分裂与融合的核心因子陆续被发现,它们在进化上高度保守,但是在形成分裂与融合复合物中的详细分子机制还有待于深入研究.线粒体分裂与融合的动态变化,是线粒体质量控制的重要组成部分,其动态平衡在细胞发育和稳态维持中起重要作用.线粒体动态变化失衡和功能失调,则会导致多种神经退行性疾病的发生.这些研究的发现为探索线粒体生物学及与疾病的关系开拓了令人振奋的新方向. | 朱笠 邓健文 王鹏 刘江红 Jane Y.Wu | 2016 | 生物化学与生物物理进展2016，43，4： | 5 |
| 2 | Expression of human FUS/TLS in yeast leads to protein aggregation and cytotoxicity,recapitulating key features of FUS proteinopathy显示文摘Mutations in the fused in sarcoma/translocated in liposarcoma(FUS/TLS)gene have been associated with amyotrophic lateral sclerosis(ALS).FUS-positive neuropathology is reported in a range of neurodegenerative diseases,including ALS and fronto-temporal lobar degeneration with ubiquitin-positive pathology(FTLDU).To examine protein aggregation and cytotoxicity,we expressed human FUS protein in yeast.Expression of either wild type or ALS-associated R524S or P525L mutant FUS in yeast cells led to formation of aggregates and cytotoxicity,with the two ALS mutants showing increased cytotoxicity.Therefore,yeast cells expressing human FUS protein recapitulate key features of FUSpositive neurodegenerative diseases.Interestingly,a significant fraction of FUS expressing yeast cells stained by propidium iodide were without detectable protein aggregates,suggesting that membrane impairment and cellular damage caused by FUS expression may occur before protein aggregates become microscopically detectable and that aggregate formation might protect cells from FUS-mediated cytotoxicity.The N-terminus of FUS,containing the QGSY and G rich regions,is sufficient for the formation of aggregates but not cytotoxicity.The C-terminal domain,which contains a cluster of mutations,did not show aggregation or cytotoxicity.Similar to TDP-43 when expressed in yeast,FUS protein has the intrinsic property of forming aggregates in the absence of other human proteins.On the other hand,the aggregates formed by FUS are thioflavin T-positive and resistant to 0.5%sarkosyl,unlike TDP-43 when expressed in yeast cells.Furthermore,TDP-43 and FUS display distinct domain requirements in aggregate formation and cytotoxicity. | Kazuo Fushimi Charles Long Neha Jayaram Xiaoping Chen Liming Li Jane Y.Wu | 2011 | Protein & Cell2011，2，2： | 4 |
| 3 | AMPK interacts with DSCAM and plays an important role in Netrin-1 induced neurite outgrowth显示文摘Down syndrome cell adhesion molecule(DSCAM)acts as a netrin-1 receptor and mediates attractive response of axons to netrin-1 in neural development.However,the signaling mechanisms of netrin-DSCAM remain unclear.Here we report that AMP-activated protein kinase(AMPK)interacts with DSCAM through itsγsubunit,but does not interact with DCC(deleted in co-lorectal cancer),another major receptor for netrin-1.Netrin-treatment of cultured cortical neurons leads to increased phosphorylation of AMPK.Both AMPK mu-tant with dominant-negative effect and AMPK inhibitor can significantly suppress netrin-1 induced neurite outgrowth.Together,these findings demonstrate that AMPK interacts with DSCAM and plays an important role in netrin-1 induced neurite outgrowth.Our study uncovers a previously unknown component,AMPK,in netrin-DSCAM signaling pathway. | Kun Zhu Xiaoping Chen Jianghong Liu Haihong Ye Li Zhu Jane Y.Wu | 2013 | Protein & Cell2013，4，2： | 1 |
| 4 | Autism, an area that needs public attention and investment显示文摘I would like to dedicate this special issue to children and adults who are affected by autism or related developmental disorders,as well as to their families and friends.I am indebted to the clinicians and care providers who have made tremendous effort in supporting these patients.They have inspired me to invest a significant amount of my energy to adventure into this area.I greatly appreciate all the contributing authors around the world whose hard work made | Jane Y.WU | 2015 | Science China(Life Sciences)2015，58，10： | 1 |
| 5 | Spliceosomal genes in the D.discoideum genome:a comparison with those in H.sapiens,D.melanogaster,A.thaliana and S.cerevisiae显示文摘Little is known about pre-mRNA splicing in Dictyostelium discoideum although its genome has been completely sequenced.Our analysis suggests that pre-mRNA splicing plays an important role in D.discoideum gene expression as two thirds of its genes contain at least one intron.Ongoing curation of the genome to date has revealed 40 genes in D.discoideum with clear evidence of alternative splicing,supporting the existence of alternative splicing in this unicellular organism.We identified 160 candidate U2-type spliceosomal proteins and related factors in D.discoideum based on 264 known human genes involved in splicing.Spliceosomal small ribonucleoproteins(snRNPs),PRP19 complex proteins and late-acting proteins are highly conserved in D.discoideum and throughout the metazoa.In non-snRNP and hnRNP families,D.discoideum orthologs are closer to those in A.thaliana,D.melanogaster and H.sapiens than to their counterparts in S.cerevisiae.Several splicing regulators,including SR proteins and CUGbinding proteins,were found in D.discoideum,but not in yeast.Our comprehensive catalog of spliceosomal proteins provides useful information for future studies of splicing in D.discoideum where the efficient genetic and biochemical manipulation will also further our general understanding of pre-mRNA splicing. | Bing Yu Petra Fey Karen E.Kestin-Pilcher Alexei Fedorov Ashwin Prakash Rex L.Chisholm Jane Y.Wu | 2011 | Protein & Cell2011，2，5： | 1 |
| 6 | Dscam mutation leads to hydrocephalus and decreased motor function显示文摘The nervous system is one of the most complicated organ systems in invertebrates and vertebrates.Down syndrome cell adhesion molecule(DSCAM)of the immunoglobulin(Ig)superfamily is expressed widely in the nervous system during embryonic development.Previous studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching,dendritic tiling and cell spacing.However,the function of the mammalian DSCAM gene in the formation of the nervous system remains unclear.Here,we show that Dscam^(del17) mutant mice exhibit severe hydrocephalus,decreased motor function and impaired motor learning ability.Our data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system. | Yiliang Xu Haihong Ye Yan Shen Qi Xu Li Zhu Jianghong Liu Jane Y.Wu | 2011 | Protein & Cell2011，2，8： | 1 |
| 7 | Expression of human FUS protein in Drosophila leads to progressive neurodegeneration显示文摘Mutations in the Fused in sarcoma/Translated in liposarcoma gene(FUS/TLS,FUS)have been identified among patients with amyotrophic lateral sclerosis(ALS).FUS protein aggregation is a major pathological hallmark of FUS proteinopathy,a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies.We prepared transgenic Drosophila expressing either the wild type(Wt)or ALS-mutant human FUS protein(hFUS)using the UAS-Gal4 system.When expressing Wt,R524S or P525L mutant FUS in photoreceptors,mushroom bodies(MBs)or motor neurons(MNs),transgenic flies show age-dependent progressive neural damages,including axonal loss in MB neurons,morphological changes and functional impairment in MNs.The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy,representing the first stable animal model for this group of devastating diseases. | Yanbo Chen Mengxue Yang Jianwen Deng Xiaoping Chen Ye Ye Li Zhu Jianghong Liu Haihong Ye Yan Shen Yan Li Elizabeth J.Rao Kazuo Fushimi Xiaohong Zhou Eileen H.Bigio Marsel Mesulam Qi Xu Jane Y.Wu | 2011 | Protein & Cell2011，2，6： | 1 |
| 8 | Neuronal guidance genes in health and diseases显示文摘Neurons migrate from their birthplaces to the destinations,and extending axons navigate to their synaptic targets by sensing various extracellular cues in spatiotemporally controlled manners.These evolutionally conserved guidance cues and their receptors regulate multiple aspects of neural development to establish the highly complex nervous system by mediating both short-and long-range cell-cell communications.Neuronal guidance genes(encoding cues,receptors,or downstream signal transducers)are critical not only for development of the nervous system but also for synaptic maintenance,remodeling,and function in the adult brain.One emerging theme is the combinatorial and complementary functions of relatively limited classes of neuronal guidance genes in multiple processes,including neuronal migration,axonal guidance,synaptogenesis,and circuit formation.Importantly,neuronal guidance genes also regulate cell migration and cell-cell communications outside the nervous system.We are just beginning to understand how cells integrate multiple guidance and adhesion signaling inputs to determine overall cellular/subcellular behavior and how aberrant guidance signaling in various cell types contributes to diverse human diseases,ranging from developmental,neuropsychiatric,and neurodegenerative disorders to cancer metastasis.We review classic studies and recent advances in understanding signaling mechanisms of the guidance genes as well as their roles in human diseases.Furthermore,we discuss the remaining chalienges and therapeutic potentials of modulating neuronal guidance pathways in neural repair. | Junichi Yuasa-Kawada Mariko Kinoshita-Kawada Yoshio Tsuboi Jane Y.Wu | 2023 | Protein & Cell2023，14，4： | 1 |
| 9 | Candidate Mycobacterium tuberculosis genes targeted by human microRNAs显示文摘Tuberculosis(TB)remains a major health issue,causing approximately three million deaths every year(Pelicic et al.,1998).Identified by Robert Koch in 1882,Mycobacterium tuberculosis(M.tuberculosis),the causative agent for tuberculosis,remains one of the most enigmatic bacteria.The interactions between M.tuberculosis and its environment have been extensively studied.However,our knowledge about potential M.tuberculosis-host interaction at the RNA level is still very limited.Here we present our preliminary finding that suggests possible interactions of human miRNAs with M.tuberculosis transcripts and speculate possible roles of human miRNAs in regulating macrophage-M.tuberculosis interactions. | WeiRui Guo Jiong-Tang Li Xiao Pan Liping Wei Jane Y.Wu | 2010 | Protein & Cell2010，1，5： | 1 |
| 10 | Progranulin promotes neurite outgrowth and neuronal differentiation by regulating GSK-3β显示文摘Progranulin(PGRN)has recently emerged as a key player in a subset of frontotemporal dementias(FTD).Numerous mutations in the progranulin gene have been identified in patients with familial or sporadic frontotemporal lobar degeneration(FTLD).In order to understand the molecular mechanisms by which PGRN deficiency leads to FTLD,we examined activity of PGRN in mouse cortical and hippocampal neurons and in human neuroblastoma SH-SY5Y cells.Treatment of mouse neurons with PGRN protein resulted in an increase in neurite outgrowth,supporting the role of PGRN as a neurotrophic factor.PGRN treatment stimulated phosphorylation of glycogen synthase kinase-3 beta(GSK-3β)in cultured neurons.Knockdown of PGRN in SH-SY5Y cells impaired retinoic acid induced differentiation and reduced the level of phosphorylated GSK-3β.PGRN knockdown cells were also more sensitized to staurosporineinduced apoptosis.These results reveal an important role of PGRN in neurite outgrowth and involvement of GSK-3βin mediating PGRN activity.Identification of GSK-3βactivation as a downstream event for PGRN signaling provides a mechanistic explanation for PGRN activity in the nervous system.Our work also suggest that loss of axonal growth stimulation during neural injury repair or deficits in axonal repair may contribute to neuronal damage or axonal loss in FTLD associated with PGRN mutations.Finally,our study suggests that modulating GSK-3βor similar signaling events may provide therapeutic benefits for FTLD cases associated with PGRN mutations. | Xue Gao Alvin P.Joselin Lei Wang Amar Kar Payal Ray Andrew Bateman Alison M.Goate Jane Y.Wu | 2010 | Protein & Cell2010，1，6： | 1 |
| 11 | Tongue as a first-line immune organ?显示文摘The tongue is an organ strategically situated at the beginning of the gastrointestinal(Gl)system,yet it has been remarkably understudied.Not only there is no separate subspecialty dedicated to the tongue,it is even excluded from 27 human organs/tissues thoroughly archived in the NCBI gene expression database.Almost none of my physician colleagues in Western medicine have paid attention to it,except a few who study tongue cancer.The tongue is typically described as a muscular organ important for taste,mastication,speech and sensation.Other than its development,anatomy/gross structural analyses and taste function(for recent reviews,see Roper and Chaudhari,2017),the human tongue is poorly studied in Western medicine,in particular,in terms of its roles in systemic diseases.In traditional Chinese medicine(TCM),however,the tongue holds a special place.Assessing the“tongue coating”,'tongue body”and morphological features is one of the most critical skills that TCM doctors have relied on for disease diagnoses for thousands of years before the advent of Western Medicine. | Jane Y.Wu | 2021 | Protein & Cell2021，12，3： | 0 |
| 12 | The splicing factor Prp31 is essential for photoreceptor development in Drosophila显示文摘Retinitis pigmentosa is a leading cause of blindness and a progressive retinal disorder,affecting millions of people worldwide.This disease is characterized by photoreceptor degeneration,eventually leading to complete blindness.Autosomal dominant(adRP)has been associated with mutations in at least four ubiquitously expressed genes encoding pre-mRNA splicing factors—Prp3,Prp8,Prp31 and PAP1.Biological function of adRPassociated splicing factor genes and molecular mechanisms by which mutations in these genes cause cell-type specific photoreceptor degeneration in humans remain to be elucidated.To investigate the in vivo function of these adRP-associated splicing factor genes,we examined Drosophila in which expression of fly Prp31 homolog was down-regulated.Sequence analyses show that CG6876 is the likely candidate of Drosophila melanogaster Prp31 homolog(DmPrp31).Predicted peptide sequence for CG6876 shows 57%similarity to the Homo sapiens Prp31 protein(HsPrp31).Reduction of the endogenous Prp31 by RNAi-mediated knockdown speci-fically in the eye leads to reduction of eye size or complete absence of eyes with remarkable features of photoreceptor degeneration and recapitulates the bimodal expressivity of human Prp31 mutations in adRP patients.Such transgenic DmPrp31RNAi flies provide a useful tool for identifying genetic modifiers or interacting genes for Prp31.Expression of the human Prp31 in these animals leads to a partial rescue of the eye phenotype.Our results indicate that the Drosophila CG6876 is the fly ortholog of mammalian Prp31 gene. | Payal Ray Xiaoyan Luo Elizabeth J.Rao Amina Basha Elvin A.Woodruff III Jane Y.Wu | 2010 | Protein & Cell2010，1，3： | 0 |
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