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分子细胞生物学报（英文版）
分子细胞生物学报（英文版）

徐永华

双月刊

1673-520X

jmcb@sibs.ac.cn，edto@sunm.shcnc.ac.cn,

021-54920951,021-54920952

200031

上海岳阳路319号31B楼

分子细胞生物学报（英文版）/Journal Journal of Molecular Cell BiologyCSCD北大核心CSTPCDSCI
查看更多>>本刊为专业学术性刊物。主要刊载有关实验生物学、动植物细胞生物学、发育生物学、生殖生物学、肿瘤生物学和免疫生物学等方面的创造性论文、简报及特约综述，反映本学科的最新研究成果。读者对象为与本学科有关的大专院校师生及医学、生物学的科研人员。
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    SV2B defines a subpopulation of synaptic vesicles

    Isabelle PaulussenHannes BeckertTimothy F.MusialLena J.Gschossmann...
    1-13页
    查看更多>>摘要：Synaptic vesicles can undergo several modes of exocytosis,endocytosis,and trafficking within individual synapses,and their fates may be linked to different vesicular protein composition.Here,we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy.SV2B is almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone.In contrast,SV2A was found in all domains of the synapse and was slightly enriched near the active zone.SV2B and SV2A were found on the membrane in the peri-active zone,suggesting recycling from both clusters of vesicles.SV2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency stimulation.Our data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial gradients.The almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found to be more important for vesicle release.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    A computational study for understanding the impact of p120-catenin on the cis-dimerization of cadherin

    Zhaoqian SuVinh H.VuDeborah E.LeckbandYinghao Wu...
    14-24页
    查看更多>>摘要：A prototype of cross-membrane signal transduction is that extracellular binding of cell surface receptors to their ligands induces intracellular signalling cascades.However,much less is known about the process in the opposite direction,called inside-out signalling.Recent studies show that it plays a more important role in regulating the functions of many cell surface receptors than we used to think.In particular,in cadherin-mediated cell adhesion,recent experiments indicate that intracellular binding of the scaffold protein p120-catenin can promote extracellular clustering of cadherin and alter its adhesive function.The underlying mechanism,however,is not well understood.To explore possible mechanisms,we designed a new multiscale simulation procedure.Using all-atom molecular dynamics simulations,we found that the conformational dynamics of the cadherin extracellular region can be altered by the intracellular binding of p120-catenin.More intriguingly,by integrating all-atom simulation results into coarse-grained random sampling,we showed that the altered conformational dynamics of cadherin caused by the binding of p120-catenin can increase the probability of lateral interactions between cadherins on the cell surface.These results suggest that p120-catenin could allosterically regulate the cis-dimerization of cadherin through two mechanisms.First,p120-catenin controls the extracellular conformational dynamics of cadherin.Second,p120-catenin oligomerization can further promote cadherin clustering.Therefore,our study provides a mechanistic foundation for the inside-out signalling in cadherin-mediated cell adhesion,while the computational framework can be generally applied to other cross-membrane signal transduction systems.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3 β-mediated preservation of mitochondrial integrity and Parkin-mediated mitophagy

    Yingmei ZhangRongjun ZouMiyesaier AbudureyimuQiong Liu...
    25-40页
    查看更多>>摘要：Mitochondrial aldehyde dehydrogenase(ALDH2)offers proven cardiovascular benefit although its impact in diabetes remains elusive.This study examined the effect of ALDH2 overexpression(OE)and knockout(KO)on diabetic cardiomyopathy and mechanism involved with a focus on mitochondrial integrity.ALDH2 OE and KO mice were challenged with streptozotocin(STZ,200 mg/kg.i.p.)to establish diabetes.Diabetic patients displayed reduced plasma ALDH2 activity,cardiac remodeling,and diastolic dysfunction.STZ challenge prompted reduced respiratory exchange ratio,dampened fractional shortening,ejection fraction,increased left ventricular(LV)end-systolic and diastolic diameters,cardiac remodeling,cardiomyocyte contractile,and intracellular Ca2 + defects(depressed peak shortening and maximal velocity of shortening/relengthening,prolonged relengthening,dampened intracellular Ca2 + rise and clearance),myocardial ultrastructural injury,oxidative stress,apoptosis,and mitochondrial damage,the effects of which were overtly attenuated and accentuated by ALDH2 OE and KO,respectively.Immunoblotting revealed downregulated mitochondrial proteins PPAR γ coactivator 1 α(PGC-1 α)and UCP-2,Ca2 + regulatory proteins including SERCA and Na+-Ca2 + exchanger,elevated phospholamban,dampened autophagy and mitophagy(LC3B ratio,TOM20,Parkin,FUNDC1,and BNIP3),disrupted phosphorylation of Akt,GSK3 β,and Foxo3a,and elevated PTEN phosphorylation,the effect of which was reversed and worsened by ALDH2 OE and KO,respectively(except FUNDC1 and BNIP3).In vivo and in vitro data revealed that novel ALDH2 activator torezolid/Alda-1 protected against STZ or high glucose-induced cardiac anomalies,the effect was nullified by inhibition of Akt,GSK3 β,Parkin,and mitochondrial coupling.Our data discerned a vital role for ALDH2 in diabetic cardiomyopathy possibly through regulation of Akt,GSK3 β activation,Parkin mitophagy,and mitochondrial function.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair

    Katrina N.EstepJohn W.TobiasRafael J.Fernandez ⅢBrinley M.Beveridge...
    41-58页
    查看更多>>摘要：Although mechanisms of telomere protection are well-defined in differentiated cells,it is poorly understood how stem cells sense and respond to telomere dysfunction.In particular,the broader impact of telomeric double-strand breaks(DSBs)in these cells is poorly characterized.Here,we report on deoxyribonucleic acid damage signaling,cell cycle,and transcriptome-level changes in human induced pluripotent stem cells(iPSCs)in response to telomere-internal DSBs.We engineered human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres.Using this model,we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response,which leads to p53-independent cell cycle arrest in G2.Using CRISPR-Cas9 to cripple the catalytic domain of telomerase,we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres,which instead are effectively repaired by robust homologous recombination(HR).In contrast to HR-based telomere maintenance in mouse embryonic stem cells,we find neither evidence that HR causes extension of telomeres beyond their initial lengths,nor an apparent role for ZSCAN4 in this process.Rather,HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length,which is compatible with sustained survival of the cells over several days of TRF1-FokI induction.Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric damage.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    ELP3 stabilizes c-myc to promote tumorigenesis

    Wentao ZhaoCong OuyangChen HuangJiaojiao Zhang...
    59-72页
    查看更多>>摘要：ELP3,the catalytic subunit of Elongator complex,is an acetyltransferase and associated with tumor progression.However,the detail of ELP3 oncogenic function remains largely unclear.Here,we found that ELP3 stabilizes c-Myc to promote tumorigenesis in an acetyltransferase-independent manner.Mechanically,ELP3 competes with the E3-ligase FBXW7 β for c-Myc binding,resulting in the inhibition of FBXW7 β-mediated ubiquitination and proteasomal degradation of c-Myc.ELP3-knockdown diminishes glycolysis and glutaminolysis and dramatically retards cell proliferation and xenograft growth by downregulating c-Myc,and such effects are rescued by reconstitution of c-Myc expression.Moreover,ELP3 and c-Myc were overexpressed with a positive correlation in colorectal cancer and hepatocellular carcinoma.Taken together,we elucidate a new function of ELP3 in promoting tumorigenesis by stabilizing c-Myc,suggesting that inhibition of ELP3 is a potential strategy for the therapy of c-Myc-driven carcinomas.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Targeting hepatic ceruloplasmin mitigates nonalcoholic steatohepatitis by modulating bile acid metabolism

    Quanxin JiangNing WangS?ia LuJie Xiong...
    73-88页
    查看更多>>摘要：Nonalcoholic steatohepatitis(NASH)is a condition that progresses from nonalcoholic fatty liver disease(NAFLD)and is characterized by hepatic fat accumulation,inflammation,and fibrosis.It has the potential to develop into cirrhosis and liver cancer,and currently no effective pharmacological treatment is available.In this study,we investigate the therapeutic potential of targeting ceruloplasmin(Cp),a copper-containing protein predominantly secreted by hepatocytes,for treating NASH.Our result show that hepatic Cp is remarkedly upregulated in individuals with NASH and the mouse NASH model.Hepatocyte-specific Cp ablation effectively attenuates the onset of dietary-induced NASH by decreasing lipid accumulation,curbing inflammation,mitigating fibrosis,and ameliorating liver damage.By employing transcriptomics and metabolomics approaches,we have discovered that hepatic deletion of Cp brings about remarkable restoration of bile acid(BA)metabolism during NASH.Hepatic deletion of Cp effectively remodels BA metabolism by upregulating Cyp7a1 and Cyp8b1,which subsequently leads to enhanced BA synthesis and notable alterations in BA profiles.In conclusion,our studies elucidate the crucial involvement of Cp in NASH,highlighting its significance as a promising therapeutic target for the treatment of this disease.
      原文链接:
    • NETL
    • NSTL
    • 万方数据