细胞分裂与细胞几何状态的交会

1、Cell Vol. 142, Issue 2, July 23, 2010Featured Articles 特辑Essay评论Cell Division Intersects with Cell Geometryp184细胞分裂与细胞几何状态的交会Featured Articles 特辑Article 研究文章NF1 Is a Tumor Suppressor in Neuroblastoma that Determines Retinoic Acid Response and Disease Outcompe218NF1 是神经母细胞瘤中决定对维甲酸反应及疾病转归的一个肿瘤抑制因子Essa

2、y评论Neocortical Interneurons: From Diversity, Strengthp189新皮层的中间神经元：从多样性和强度说起Articles 研究文章1. SRD5A3 Is Required for Converting Polyprenol to Dolichol and IsMutated in a Congenital Glycosylation Disorderp203为多菇醇向长醇的转化所必须的SRD5A3在先天性糖基化障碍性疾病中发生突变2. TRF2 and Apollo Cooperate with Topoisomerase 2 a to Pro

3、tect Human Telomeres from Replicative Damagep230TRF2、Apollo与拓扑异构酶2 a协同保护人类端粒免受复制损伤3. Crossover Invariance Determined by Partner Choice for Meiotic DNABreak Repair p243减数分裂 DNA 断裂修补中伴侣选择规律所决定的交叉频率恒定性4. A Surveillance Pathway Monitors the Fitness of the Endoplasmic Reticulum to Control Its Inheritance

4、p256一个监视通路监测内质网的健康情况并依此控制其遗传性5. Essential Regulation of Cell Bioenergetics by Constitutive In3sPReceptor Ca2+ Transfer to Mitochondria p270从组成型InsR受体到线粒体的Ca2+转移对细胞生物能学的调节至关重要6. External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectorsinto Plant and Animal Host Cellsp284外在脂质成份PI3P介导真核病原效应因子

5、进入植物及动物宿主细胞的过程7. Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolismp296成骨细胞中的胰岛素信号通路整合骨重塑与能量代谢过程8. Insulin Receptor Signaling in Osteoblasts Regulates Postnatal Bone Acquisition and Body Compositiorp309成骨细胞中的胰岛素受体信号通路调节出生后骨质的获取及身体的构成9. SIRT1 Suppresses -Amyloid Product

6、ion by Activating the -Secretase Gene ADAM10 p320SIRT1通过激活优分泌酶基因ADAM10抑制自淀粉样肽的合成Snapshot 快照Enhanced Snapshot: Pore-Forming Toxins)334升级版Snapshot成孔毒素Featured Articles 特辑Essay评论Cell Division Intersects with Cell Geometryp184细胞分裂与细胞几何状态的交会James B. Moseley, Paul NurseSummary: Single-celled organisms mon

7、itor cell geometry and use this information to control cell division. Such geometry-sensing mechanisms control both the decision to enter into cell division and the physical orientation of the chromosome segregation machinery, suggesting that signals controlling cell division may be linked to the me

8、chanisms that ensure proper chromosome segregation.Featured Articles 特辑Article研究文章NF1 Is a Tumor Suppressor in Neuroblastoma that Determines Retinoic Acid Response and Disease Outcomp218NF1是神经母细胞瘤中决定对维甲酸反应及疾病转归的一个月中瘤抑制因子 Michael H?lzel, Sidong Huang, Jan Koster, Ingrid ?ra, Arjan Lakeman, Huib Caron

9、, Wouter Nijkamp, Jing Xie, Tom Callens, Shahab Asgharzadeh, Robert C. Seeger, Ludwine Messiaen, Rogier Versteeg, Ren BernardsHighlights:, Loss of NF1 blocks retinoic acid (RA) induced differentiation in neuroblastoma Loss of NF1 represses the RA receptor coactivator ZNF423 through RAS- MEK signalin

10、g, Mutations and low expression of NF1 occur in primary neuroblastomas MEK inhibitors restore the RA response in NFI-deficient neuroblastomasSummary: Retinoic acid (RA) induces differentiation of neuroblastoma cellsin vitro and is used with variable success to treat aggressive forms of this disease.

11、 This variability in clinical response to RA is enigmatic, as no mutations in components of the RA signaling cascade have been found. Using a large-scale RNAi genetic screen, we identify crosstalk between the tumor suppressoNF1 and retinoic acid-induced differentiation in neuroblastoma. Loss ofNF1 a

12、ctivates RAS-MEK signaling, which in turn represses ZNF423, a critical transcriptional coactivator of the retinoic acid receptors. Neuroblastomas with low levels of bothNF1 and ZNF423 have extremely poor outcome. We find NF1 mutations in neuroblastoma cell lines and in primary tumors. Inhibition of

13、MEK signaling downstream of NF1 restores responsiveness to RA, suggesting a therapeutic strategy to overcome RA resistance NnF1-deficient neuroblastomas.Essay评论Neocortical Interneurons: From Diversity, Strengthp189 新皮层的中间神经元：从多样性和强度说起Christopher I. Moore, Marie Carlen, Ulf Knoblich, Jessica A. Cardi

14、nSummary: Interneurons in the neocortex of the brain are small, locally projecting inhibitory GABAergic cells with a broad array of anatomical and physiological properties. The diversity of interneurons is believed to be crucial for regulating myriad operations in the neocortex. Here, we describe cu

15、rrent theories about how interneuron diversity may support distinct neocortical processes that underlie perception.Articles研究文章1. SRD5A3 Is Required for Converting Polyprenol to Dolichol and Is Mutated in a Congenital Glycosylation Disorderp203为多菇醇向长醇的转化所必须的SRD5A3在先天性糖基化障碍性疾病中发生突变Vincent Cantagrel,

16、Dirk J. Lefeber, Bobby G. Ng, Ziqiang Guan, Jennifer L. Silhavy, Stephanie L. Bielas, Ludwig Lehle, Hans Hombauer, Maciej Adamowicz, Ewa Swiezewska, Arjan P. De Brouwer, Peter Bl mel, Jolanta Sykut-Cegielska, Scott Houliston, Dominika Swistun, Bassam R. Ali, William B. Dobyns, Dusica Babovic-Vuksano

17、vic, Hans van Bokhoven, Ron A. Wevers, Christian R.H. Raetz, Hudson H. Freeze, va Morava, Lihadh Al-Gazali, Joseph G. GleesonHighlights: SRD5A3mutations in human cause a new congenital disorder of glycosylation SRD5A3 is involved in the synthesis of dolichol, the carrier of oligosaccharide SRD5A3 fu

18、nction in N-glycosylation is evolutionary conserved in eukaryotic cells SRD5A3 is necessary for the reduction of the terminal isoprene unit of polyprenolSummary: N-linked glycosylation is the most frequent modification of secreted and membrane-bound proteins in eukaryotic cells, disruption of which

19、is the basis of the congenital disorders of glycosylation (CDGs). We describe a new type of CDG caused by mutations in thesteroid 5 -reductase type 3(SRD5A3 gene. Patients have mental retardation and ophthalmologic and cerebellar defects. We found that SRD5A3 is necessary for the reduction of the al

20、pha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide precursor used for N-glycosylation. The presence of residual dolichol in cells depleted for this enzyme suggests the existence of an unexpected alternative pathway f

21、or dolichol de novo biosynthesis. Our results thus suggest that SRD5A3 is likely to be the long-sought polyprenol reductase and reveal the genetic basis of one of the earliest steps in protein N-linked glycosylation.2. TRF2 and Apollo Cooperate with Topoisomerase 2 a to Protect Human Telomeres from

22、Replicative Damageo230TRF2、Apollo与拓扑异构酶2 a协同保护人类端粒免受复制损伤 Jing Ye, Christelle Lenain, Serge Bauwens, Angela Rizzo, Adelade Saint-L ger, Ana& Poulet, Delphine Benarroch, Fr d Kique Magdinier, Julia Morere, Simon Amiard, Els Verhoeyen, S bastien Britton, Patrick Calsou, Bernard Salles, Anna Bizard,

23、 Marc Nadal, Erica Salvati, Laure Sabatier, Yunlin Wu, Annamaria Biroccio, Arturo Londo? o-Vallejo, Marie-Jos phe Giraud-Panis, Eric GilsonHighlights: Replication through telomeric DNA requires TRF2 and the nuclease domain of Apollo DNA topoisomerase 2 a protects telomeres in the same pathway as TRF

24、2 and Apollo TRF2 preferentially binds positive supercoiled DNA Apollo and TRF2 control the amount of topoisomerase needed for telomere replicationSummary: Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2

25、 regulates the 5 exonuclease activity of its binding partner, Apollo, a member of the metallo- lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome e

26、nds. Genetic data indicate that DNA topoisomerase 2 a acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1T OP2x , and TOP2 0 at telomeres

27、. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres.3. Crossover Invariance De

28、termined by Partner Choice for Meiotic DNA Break Repair p243减数分裂DNA断裂修补中伴侣选择规律所决定的交叉频率恒定性 Randy W. Hyppa, Gerald R. SmithHighlights: Meiotic DSBs occur at chromosomal hotspots; fission yeast crossovers are more uniform At DSB hotspots Holliday junctions are formed primarily with the sister, without

29、Dmc1 In cold regions, Holliday junctions are formed with the homolog and require Dmc1 Partner choice for DSB repair largely accounts for the observed crossover invarianceSummary: Crossovers between meiotic homologs are crucial for their proper segregation, and crossover number and position are caref

30、ully controlled. Crossover homeostasis in budding yeast maintains crossovers at the expense of noncrossovers when double-strand DNA break (DSB) frequency is reduced. The mechanism of maintaining constant crossover levels in other species has been unknown. Here we investigate in fission yeast a diffe

31、rent aspect of crossover controlthe near invariance of crossover frequency per kb of DNA despite large variations in DSB intensity across the genome. Crossover invariance involves the choice of sister chromatid versus homolog for DSB repair. At strong DSB hotspots, intersister repair outnumbers inte

32、rhomolog repair 3:1, but our genetic and physical data indicate the converse in DSB-cold regions. This unanticipated mechanism of crossover control may operate in many species and explain, for example, the large excess of DSBs over crossovers and the repair of DSBs on unpaired chromosomes in diverse

33、 species.4. A Surveillance Pathway Monitors the Fitness of the Endoplasmic Reticulum to Control Its Inheritancep256一个监视通路监测内质网的健康情况并依此控制其遗传性 Anna Babour, Alicia A. Bicknell, Joel Tourtellotte, Maho NiwaHighlights: Cells monitor the functionality of the endoplasmic reticulum during the cell cycle End

34、oplasmic eeticulum (ER) stress is recognized by a ER surveillance (ERSU) pathway ERSU induces delayed cortical ER inheritance and cytokinesis in response to ER stress ERSU signaling is essential for generation of viable progeny during ER stressSummary: The endoplasmic reticulum (ER) plays an essenti

35、al role in the production of lipids and secretory proteins. Because the ER cannot be generated de novo, it must be faithfully transmitted or divided at each cell division. Little is known of how cells monitor the functionality of the ER during the cell cycle or how this regulates inheritance. We rep

36、ort here that ER stress iS. cerevisiaeactivates the MAP kinase Slt2 in a new ER stress surveillance (ERSU) pathway, independent of the unfolded protein response. Upon ER stress, ERSU alters the septin complex to delay ER inheritance and cytokinesis. In the absence of Slt2 kinase, the stressed ER is

37、transmitted to the daughter cell, causing the death of both mother and daughter cells. Furthermore, Slt2 is activated via the cell surface receptor Wsc1 by a previouslyundescribed mechanism. We conclude that the ERSU pathway ensures inheritance of a functional ER.5. Essential Regulation of Cell Bioe

38、nergetics by Constitutive Ins Receptor Ca2+ Transfer to Mitochondria p270从组成型InsP3受体到线粒体的Ca2+转移对细胞生物能学的调节至关重要Cesar C rdenas, Russell A. Miller, Ian Smith, Thi Bui, Jordi Molg , Marioly M llerp Horia Vais, King-Ho Cheung, Jun Yang, Ian Parker, Craig B. Thompson, Morris J. Birnbaum, Kenneth R. Hallows

39、, J. Kevin FoskettHighlights: Constitutive InsP3R Ca2+ release suppresses autophagy in nutrient-rich conditions Absence of constitutive InsRR Ca2+ release reduces cell ATP and activates AMP kinase Mitochondrial uptake of released Ca+ is required for sufficient ATP production Constitutive ER-to-mitoc

40、hondria Ca2+ transfer is essential for normal bioenergeticsSummary: Mechanisms that regulate cellular metabolism are a fundamental requirement of all cells. Most eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Nevertheless, regulation of mitochondrial activity is incomplet

41、ely understood. Here we identified an unexpected and essential role for constitutive InsP3R-mediated C4+ release in maintaining cellular bioenergetics.Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP3R Ca2+ signaling is re

42、quired for macroautophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to diminished mitochondrial Ca+ uptake.2+ .Mitochondrial uptake of InsPsR-released Ca is fundamentally required to provide optimal bioenergetics by providing sufficien

43、t reducing equivalents to support oxidative phosphorylation. Absence of this C02+ transfer results in enhanced phosphorylation of pyruvate dehydrogenase and activation of AMPK, which activates prosurvival macroautophagy. Thus, constitutive InsPR C#+ release to mitochondria is an essential cellular p

44、rocess that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics.6. External Lipid PI3P Mediates Entry of Eukaryotic Pathogen Effectors into Plant and Animal Host Cellsp284外在脂质成份PI3P介导真核病原效应因子进入植物及动物宿主细胞的过程 Shiv D. Kale, Biao Gu, Daniel G.S. Capelluto, Dao

45、long Dou, Emily Feldman, Amanda Rumore, Felipe D. Arredondo, Regina Hanlon, Isabelle Fudal, Thierry Rouxel, Christopher B. Lawrence, Weixing Shan口，Brett M. Tyler 口Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USACollege of Plant Protect

46、ion and Shaanxi Key Laboratory of Molecular Biology for Agriculture, Northwest A & F University, Yangling, Shaanxi 712100, China 陕西杨林西北农林科技大学Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USAINRA-Bioger, Campus AgroParisTech, 78850 T

47、hiverval-Grignon, France Corresponding author Present address: Department of Plant Pathology, Nanjing Agricultural University, Nanjing 210095, China通讯作者之一：单卫星教授。现地址：南京农业大学植物病理系Highlights: Oomycete and fungal pathogen effectors bind PI3P via their host cell entry motifs PI3P is abundant on the surfac

48、e of plant cells and some human cells Binding to PI3P is required for host cell entry via lipid raft-mediated endocytosis Blocking of effector entry by exogenous molecules suggests therapeutic strategiesSummary: Pathogens of plants and animals produce effector proteins that are transferred into the

49、cytoplasm of host cells to suppress host defenses. One type of plant pathogens, oomycetes, produces effector proteins with N-terminal RXLR and dEER motifs that enable entry into host cells. We show here that effectors of another pathogen type, fungi, contain functional variants of the RXLR motif, an

50、d that the oomycete and fungal RXLR motifs enable binding to the phospholipid, phosphatidylinositol-3-phosphate (PI3P). We find that PI3P is abundant on the outer surface of plant cell plasma membranes and, furthermore, on some animal cells. All effectors could also enter human cells, suggesting tha

51、t PI3P-mediated effector entry may be very widespread in plant, animal and human pathogenesis. Entry into both plant and animal cells involves lipid raft-mediated endocytosis. Blocking PI3P binding inhibited effector entry, suggesting new therapeutic avenues.7. Insulin Signaling in Osteoblasts Integ

52、rates Bone Remodeling and Energy Metabolismp296成骨细胞中的胰岛素信号通路整合骨重塑与能量代谢过程 Mathieu Ferron, Jianwen Wei, Tatsuya Yoshizawa, Andrea Del Fattore, Ronald A. DePinho, Anna Teti, Patricia Ducy, Gerard KarsentyHighlights: Insulin signaling in mouse osteoblasts increases activity of the hormone osteocalcin Os

53、teocalcin activation depends on the acidic pH in the bone resorption area Enhanced osteocalcin activity promotes glucose metabolism via bone resorption, Regulation of glucose metabolism by bone also occurs in humansSummary: The broad expression of the insulin receptor suggests that the spectrum of i

54、nsulin function has not been fully described. A cell type expressing this receptor is the osteoblast, a bone-specific cell favoring glucose metabolism through a hormone, osteocalcin, that becomes active once uncarboxylated. We show here that insulin signaling in osteoblasts is necessary for whole-bo

55、dy glucose homeostasis because it increases osteocalcin activity. To achieve this function insulin signaling in osteoblasts takes advantage of the regulation of osteoclastic bone resorption exerted by osteoblasts. Indeed, since bone resorption occurs at a pH acidic enough to decarboxylate proteins,

56、osteoclasts determine the carboxylation status and function of osteocalcin. Accordingly, increasing or decreasing insulin signaling in osteoblasts promotes or hampers glucose metabolism in a bone resorption-dependent manner in mice and humans. Hence, in a feed-forward loop, insulin signals in osteob

57、lasts activate a hormone, osteocalcin, that promotes glucose metabolism.8. Insulin Receptor Signaling in Osteoblasts Regulates Postnatal Bone Acquisition and Body Compositiorp309成骨细胞中的胰岛素受体信号通路调节出生后骨质的获取及身体的构成 Keertik Fulzele, Ryan C. Riddle, Douglas J. DiGirolamo, Xuemei Cao, Chao Wan, Dongquan Che

58、n, Marie-Claude Faugere, Susan Aja, Mehboob A. Hussain, Jens C. Br tning, Thomas L. ClemensHighlights: Insulin signaling in osteoblasts is required for normal bone acquisition Insulin stimulates osteoblast production of the insulin secretagogue osteocalcin Mice lacking IR in osteoblasts develop peri

59、pheral insulin resistance Osteocalcin infusion improves insulin sensitivity in mutant IR mice Summary: Global energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated,