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Nature Cell Biology

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https://read.qxmd.com/read/30988424/ultrastructure-and-dynamics-of-the-actin-myosin-ii-cytoskeleton-during-mitochondrial-fission
#1
Changsong Yang, Tatyana M Svitkina
Mitochondrial fission involves the preconstriction of an organelle followed by scission by dynamin-related protein Drp1. Preconstriction is facilitated by actin and non-muscle myosin II through a mechanism that remains unclear, largely due to the unknown cytoskeletal ultrastructure at mitochondrial constrictions. Here, using platinum replica electron microscopy, we show that mitochondria in cells are embedded in an interstitial cytoskeletal network that contains abundant unbranched actin filaments. Both spontaneous and induced mitochondrial constrictions typically associate with a criss-cross array of long actin filaments that comprise part of this interstitial network...
April 15, 2019: Nature Cell Biology
https://read.qxmd.com/read/30988423/bone-vascular-niche-e-selectin-induces-mesenchymal-epithelial-transition-and-wnt-activation-in-cancer-cells-to-promote-bone-metastasis
#2
Mark Esposito, Nandini Mondal, Todd M Greco, Yong Wei, Chiara Spadazzi, Song-Chang Lin, Hanqiu Zheng, Corey Cheung, John L Magnani, Sue-Hwa Lin, Ileana M Cristea, Robert Sackstein, Yibin Kang
How disseminated tumour cells engage specific stromal components in distant organs for survival and outgrowth is a critical but poorly understood step of the metastatic cascade. Previous studies have demonstrated the importance of the epithelial-mesenchymal transition in promoting the cancer stem cell properties needed for metastasis initiation, whereas the reverse process of mesenchymal-epithelial transition is required for metastatic outgrowth. Here we report that this paradoxical requirement for the simultaneous induction of both mesenchymal-epithelial transition and cancer stem cell traits in disseminated tumour cells is provided by bone vascular niche E-selectin, whose direct binding to cancer cells promotes bone metastasis by inducing mesenchymal-epithelial transition and activating Wnt signalling...
April 15, 2019: Nature Cell Biology
https://read.qxmd.com/read/30988422/engineering-a-haematopoietic-stem-cell-niche-by-revitalizing-mesenchymal-stromal-cells
#3
Fumio Nakahara, Daniel K Borger, Qiaozhi Wei, Sandra Pinho, Maria Maryanovich, Ali H Zahalka, Masako Suzuki, Cristian D Cruz, Zichen Wang, Chunliang Xu, Philip E Boulais, Avi Ma'ayan, John M Greally, Paul S Frenette
Haematopoietic stem cells (HSCs) are maintained by bone marrow niches in vivo1,2 , but the ability of niche cells to maintain HSCs ex vivo is markedly diminished. Expression of niche factors by Nestin-GFP+ mesenchymal-derived stromal cells (MSCs) is downregulated upon culture, suggesting that transcriptional rewiring may contribute to this reduced HSC maintenance potential. Using an RNA sequencing screen, we identified five genes encoding transcription factors (Klf7, Ostf1, Xbp1, Irf3 and Irf7) that restored HSC niche function in cultured bone marrow-derived MSCs...
April 15, 2019: Nature Cell Biology
https://read.qxmd.com/read/30971772/author-correction-a-lipid-based-partitioning-mechanism-for-selective-incorporation-of-proteins-into-membranes-of-hiv-particles
#4
Prabuddha Sengupta, Arnold Y Seo, H Amalia Pasolli, Yul Eum Song, Marc C Johnson, Jennifer Lippincott-Schwartz
In the version of this article originally published, the name of co-author Marc C. Johnson was missing the middle initial. The middle initial 'C.' has been added in the author list as well as in the 'author contributions' section (as M.C.J.). The error has been corrected in the PDF and HTML versions of the paper.
April 10, 2019: Nature Cell Biology
https://read.qxmd.com/read/30962575/a-complex-containing-lysine-acetylated-actin-inhibits-the-formin-inf2
#5
Mu A, Tak Shun Fung, Arminja N Kettenbach, Rajarshi Chakrabarti, Henry N Higgs
Inverted formin 2 (INF2) is a member of the formin family of actin assembly factors. Dominant missense mutations in INF2 are linked to two diseases: focal segmental glomerulosclerosis, a kidney disease, and Charcot-Marie-Tooth disease, a neuropathy. All of the disease mutations map to the autoinhibitory diaphanous inhibitory domain. Interestingly, purified INF2 is not autoinhibited, suggesting the existence of other cellular inhibitors. Here, we purified an INF2 inhibitor from mouse brain tissue, and identified it as a complex of lysine-acetylated actin (KAc-actin) and cyclase-associated protein (CAP)...
April 8, 2019: Nature Cell Biology
https://read.qxmd.com/read/30962574/alox12-is-required-for-p53-mediated-tumour-suppression-through-a-distinct-ferroptosis-pathway
#6
Bo Chu, Ning Kon, Delin Chen, Tongyuan Li, Tong Liu, Le Jiang, Shujuan Song, Omid Tavana, Wei Gu
It is well established that ferroptosis is primarily controlled by glutathione peroxidase 4 (GPX4). Surprisingly, we observed that p53 activation modulates ferroptotic responses without apparent effects on GPX4 function. Instead, ALOX12 inactivation diminishes p53-mediated ferroptosis induced by reactive oxygen species stress and abrogates p53-dependent inhibition of tumour growth in xenograft models, suggesting that ALOX12 is critical for p53-mediated ferroptosis. The ALOX12 gene resides on human chromosome 17p13...
April 8, 2019: Nature Cell Biology
https://read.qxmd.com/read/30914825/author-correction-recapitulating-endocrine-cell-clustering-in-culture-promotes-maturation-of-human-stem-cell-derived-%C3%AE-cells
#7
Gopika G Nair, Jennifer S Liu, Holger A Russ, Stella Tran, Michael S Saxton, Richard Chen, Charity Juang, Mei-Lan Li, Vinh Q Nguyen, Simone Giacometti, Sapna Puri, Yuan Xing, Yong Wang, Gregory L Szot, Jose Oberholzer, Anil Bhushan, Matthias Hebrok
In the version of this article originally published, the Gene Expression Omnibus (GEO) accession number listed in the data availability section was incorrectly given as GSE10979 instead of GSE109795. The sentence should read "RNA-seq data that support the findings of this study have been deposited in the Gene Expression Omnibus (GEO) under accession code GSE109795," and the code should link to https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE109795. The error has been corrected in the HTML and PDF versions of the paper...
March 26, 2019: Nature Cell Biology
https://read.qxmd.com/read/30886346/a-nuclear-phosphoinositide-kinase-complex-regulates-p53
#8
Suyong Choi, Mo Chen, Vincent L Cryns, Richard A Anderson
The tumour suppressor p53 (encoded by TP53) protects the genome against cellular stress and is frequently mutated in cancer. Mutant p53 acquires gain-of-function oncogenic activities that are dependent on its enhanced stability. However, the mechanisms by which nuclear p53 is stabilized are poorly understood. Here, we demonstrate that the stability of stress-induced wild-type and mutant p53 is regulated by the type I phosphatidylinositol phosphate kinase (PIPKI-α (also known as PIP5K1A)) and its product phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2 )...
March 18, 2019: Nature Cell Biology
https://read.qxmd.com/read/30886345/mitochondrial-protein-induced-stress-triggers-a-global-adaptive-transcriptional-programme
#9
Felix Boos, Lena Krämer, Carina Groh, Ferris Jung, Per Haberkant, Frank Stein, Florian Wollweber, Adrian Gackstatter, Eva Zöller, Martin van der Laan, Mikhail M Savitski, Vladimir Benes, Johannes M Herrmann
The cytosolic accumulation of mitochondrial precursors is hazardous to cellular fitness and is associated with a number of diseases. However, it is not observed under physiological conditions. Individual mechanisms that allow cells to avoid cytosolic accumulation of mitochondrial precursors have recently been discovered, but their interplay and regulation remain elusive. Here, we show that cells rapidly launch a global transcriptional programme to restore cellular proteostasis after induction of a 'clogger' protein that reduces the number of available mitochondrial import sites...
March 18, 2019: Nature Cell Biology
https://read.qxmd.com/read/30886344/therapeutic-targeting-of-macrophages-enhances-chemotherapy-efficacy-by-unleashing-type-i-interferon-response
#10
Camilla Salvagno, Metamia Ciampricotti, Sander Tuit, Cheei-Sing Hau, Antoinette van Weverwijk, Seth B Coffelt, Kelly Kersten, Kim Vrijland, Kevin Kos, Thomas Ulas, Ji-Ying Song, Chia-Huey Ooi, Dominik Rüttinger, Philippe A Cassier, Jos Jonkers, Joachim L Schultze, Carola H Ries, Karin E de Visser
Recent studies have revealed a role for macrophages and neutrophils in limiting chemotherapy efficacy; however, the mechanisms underlying the therapeutic benefit of myeloid-targeting agents in combination with chemotherapy are incompletely understood. Here, we show that targeting tumour-associated macrophages by colony-stimulating factor-1 receptor (CSF-1R) blockade in the K14cre;Cdh1F/F ;Trp53F/F transgenic mouse model for breast cancer stimulates intratumoural type I interferon (IFN) signalling, which enhances the anticancer efficacy of platinum-based chemotherapeutics...
March 18, 2019: Nature Cell Biology
https://read.qxmd.com/read/30858581/ampk-mediated-activation-of-mcu-stimulates-mitochondrial-ca-2-entry-to-promote-mitotic-progression
#11
Haixin Zhao, Teng Li, Kai Wang, Fei Zhao, Jiayi Chen, Guang Xu, Jie Zhao, Ting Li, Liang Chen, Lin Li, Qing Xia, Tao Zhou, Hui-Yan Li, Ai-Ling Li, Toren Finkel, Xue-Min Zhang, Xin Pan
The capacity of cells to alter bioenergetics in response to the demands of various biological processes is essential for normal physiology. The coordination of energy sensing and production with highly energy-demanding cellular processes, such as cell division, is poorly understood. Here, we show that a cell cycle-dependent mitochondrial Ca2+ transient connects energy sensing to mitochondrial activity for mitotic progression. The mitochondrial Ca2+ uniporter (MCU) mediates a rapid mitochondrial Ca2+ transient during mitosis...
March 11, 2019: Nature Cell Biology
https://read.qxmd.com/read/30842593/author-correction-the-rho-gtpase-rnd1-suppresses-mammary-tumorigenesis-and-emt-by-restraining-ras-mapk-signalling
#12
Tomoyo Okada, Surajit Sinha, Ilaria Esposito, Gaia Schiavon, Miguel A López-Lago, Wenjing Su, Christine A Pratilas, Cristina Abele, Jonathan M Hernandez, Masahiro Ohara, Morihito Okada, Agnes Viale, Adriana Heguy, Nicholas D Socci, Anna Sapino, Venkatraman E Seshan, Stephen Long, Giorgio Inghirami, Neal Rosen, Filippo G Giancotti
In the version of this Article originally published the same blot was inadvertently presented as both p-Rb and Cyclin A in Fig. 2a. This blot corresponds to the p-Rb panel, as can be seen in the unprocessed version of these blots in Supplementary Fig. 9. The corrected version of the panel is shown below, together with a completely uncropped image of both blots. In addition, in the 'Viral transduction' section of the Methods, the pLKO.1 plasmids encoding short hairpin RNAs targeting human Rnd1 were incorrectly listed as clones TRCN0000018338 and TRCN0000039977...
March 6, 2019: Nature Cell Biology
https://read.qxmd.com/read/30833696/author-correction-bmi1-is-essential-in-twist1-induced-epithelial-mesenchymal-transition
#13
Muh-Hwa Yang, Dennis Shin-Shian Hsu, Hsei-Wei Wang, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Yang, Chi-Hung Huang, Shou-Yen Kao, Cheng-Hwai Tzeng, Shyh-Kuan Tai, Shyue-Yih Chang, Oscar Kuang-Sheng Lee, Kou-Juey Wu
In the version of Supplementary Fig. 3c originally published with this Article, the authors mistakenly duplicated a blot from Supplementary Fig. 3b. The correct versions of these figures are shown below. In addition, two independent repeats of the experiments presented in Supplementary Figs. 3b and 3c, showing results consistent with those originally reported, have been deposited in Figshare ( 10.6084/m9.figshare.7545263 ).
March 4, 2019: Nature Cell Biology
https://read.qxmd.com/read/30820041/author-correction-microrna-146a-directs-the-symmetric-division-of-snail-dominant-colorectal-cancer-stem-cells
#14
Wei-Lun Hwang, Jeng-Kae Jiang, Shung-Haur Yang, Tse-Shun Huang, Hsin-Yi Lan, Hao-Wei Teng, Chih-Yung Yang, Ya-Ping Tsai, Chi-Hung Lin, Hsei-Wei Wang, Muh-Hwa Yang
In the version of Supplementary Fig. 6c originally published with this Article, the immunoprecipitation (IP) and immunoblotting (IB) tags in the top panel were mislabelled. In addition, in Supplementary Fig. 6e, the blot of the IP: Numb; IB: β-Trcp panel for HCT15 was mistakenly duplicated for HCT116. The correct versions of these figures are shown below. An independent repeat of the experiments presented in Supplementary Fig. 6c and e, showing results that are consistent with those reported in the unprocessed blots, have been deposited in figshare ( 10...
February 28, 2019: Nature Cell Biology
https://read.qxmd.com/read/30808996/author-correction-per2-induction-limits-lymphoid-biased-haematopoietic-stem-cells-and-lymphopoiesis-in-the-context-of-dna-damage-and-ageing
#15
Jianwei Wang, Yohei Morita, Bing Han, Silke Niemann, Bettina Löffler, K Lenhard Rudolph
In the version of this Article originally published, the authors mistakenly used the same images for the Fig. 2d Per-/- upper Merge, DAPI and p-RPA2 (Ser33), and Fig. 3e upper 2 months, WT Per2 DAPI and Merge panels. The correct images from these experiments, and their correctly sized scale bars, are shown below. In addition, the full dataset of representative images for Figs 2d and 3e, and the numerical source data of the corresponding quantifications of Figs 2c and 3f, have been uploaded to Figshare ( https://doi...
February 26, 2019: Nature Cell Biology
https://read.qxmd.com/read/30804506/53bp1-nuclear-bodies-enforce-replication-timing-at-under-replicated-dna-to-limit-heritable-dna-damage
#16
Julian Spies, Claudia Lukas, Kumar Somyajit, Maj-Britt Rask, Jiri Lukas, Kai John Neelsen
Failure to complete DNA replication is a stochastic by-product of genome doubling in almost every cell cycle. During mitosis, under-replicated DNA (UR-DNA) is converted into DNA lesions, which are inherited by daughter cells and sequestered in 53BP1 nuclear bodies (53BP1-NBs). The fate of such cells remains unknown. Here, we show that the formation of 53BP1-NBs interrupts the chain of iterative damage intrinsically embedded in UR-DNA. Unlike clastogen-induced 53BP1 foci that are repaired throughout interphase, 53BP1-NBs restrain replication of the embedded genomic loci until late S phase, thus enabling the dedicated RAD52-mediated repair of UR-DNA lesions...
February 25, 2019: Nature Cell Biology
https://read.qxmd.com/read/30804505/apical-basal-polarity-inhibits-epithelial-mesenchymal-transition-and-tumour-metastasis-by-par-complex-mediated-snai1-degradation
#17
Hae-Yun Jung, Laurent Fattet, Jeff H Tsai, Taketoshi Kajimoto, Qiang Chang, Alexandra C Newton, Jing Yang
Loss of apical-basal polarity and activation of epithelial-mesenchymal transition (EMT) both contribute to carcinoma progression and metastasis. Here, we report that apical-basal polarity inhibits EMT to suppress metastatic dissemination. Using mouse and human epithelial three-dimensional organoid cultures, we show that the PAR-atypical protein kinase C (aPKC) polarity complex inhibits EMT and invasion by promoting degradation of the SNAIL family protein SNAI1. Under intact apical-basal polarity, aPKC kinases phosphorylate S249 of SNAI1, which leads to protein degradation...
February 25, 2019: Nature Cell Biology
https://read.qxmd.com/read/30804504/ubiquilins-regulate-autophagic-flux-through-mtor-signalling-and-lysosomal-acidification
#18
Mümine Şentürk, Guang Lin, Zhongyuan Zuo, Dongxue Mao, Emma Watson, Antonios G Mikos, Hugo J Bellen
Although the aetiology of amyotrophic lateral sclerosis (ALS) remains poorly understood, impaired proteostasis is a common feature of different forms of ALS. Mutations in genes encoding ubiquilins, UBQLN2 and UBQLN4, cause familial ALS. The role of ubiquilins in proteasomal degradation is well established, but their role in autophagy-lysosomal clearance is poorly defined. Here, we describe a crosstalk between endoplasmic reticulum stress, mTOR signalling and autophagic flux in Drosophila and mammalian cells lacking ubiquilins...
February 25, 2019: Nature Cell Biology
https://read.qxmd.com/read/30804503/a-microrna-inducible-crispr-cas9-platform-serves-as-a-microrna-sensor-and-cell-type-specific-genome-regulation-tool
#19
Xi-Wen Wang, Lu-Feng Hu, Jing Hao, Le-Qi Liao, Ya-Tzu Chiu, Ming Shi, Yangming Wang
microRNAs (miRNAs) are small noncoding RNAs that play important regulatory roles in plants, animals and viruses. Measuring miRNA activity in vivo remains a big challenge. Here, using an miRNA-mediated single guide RNA (sgRNA)-releasing strategy and dCas9-VPR to drive a transgene red fluorescent protein, we create an miRNA sensor that can faithfully measure miRNA activity at cellular levels and use it to monitor differentiation status of stem cells. Furthermore, by designing sgRNAs to target endogenous loci, we adapted this system to control the expression of endogenous genes or mutate specific DNA bases upon induction by cell-type-specific miRNAs...
February 25, 2019: Nature Cell Biology
https://read.qxmd.com/read/30783264/author-correction-sin1-phosphorylation-impairs-mtorc2-complex-integrity-and-inhibits-downstream-akt-signalling-to-suppress-tumorigenesis
#20
Pengda Liu, Wenjian Gan, Hiroyuki Inuzuka, Adam S Lazorchak, Daming Gao, Omotooke Arojo, Dou Liu, Lixin Wan, Bo Zhai, Yonghao Yu, Min Yuan, Byeong Mo Kim, Shavali Shaik, Suchithra Menon, Steven P Gygi, Tae Ho Lee, John M Asara, Brendan D Manning, John Blenis, Bing Su, Wenyi Wei
In the version of this Article originally published, the labels for Rictor and mTOR in the whole cell lysate (WCL) blots were swapped in Fig. 3b and the mTOR blot was placed upside down. Unprocessed blots of mTOR were also missing from Supplementary Fig. 9. The corrected Figs are shown below. In addition, control blots for the mTOR antibody (Cell Signalling Technology #2972) were also missing. These are now provided below, as Fig. 9, and show that the lower band is likely non-specific.
February 19, 2019: Nature Cell Biology
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