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https://www.readbyqxmd.com/read/28636948/pten%C3%AE-modulates-camkii-signaling-and-controls-contextual-fear-memory-and-spatial-learning
#1
Pan Wang, Fan Mei, Jiapan Hu, Minglu Zhu, Hailong Qi, Xi Chen, Ruiqi Li, Michael A McNutt, Yuxin Yin
PTEN (phosphatase and tensin homology deleted on chromosome 10) has multiple functions, and recent studies have shown that the PTEN family has isoforms. The roles of these PTEN family members in biologic activities warrant specific evaluation. Here, we show that PTENα maintains CaMKII in a state that is competent to induce long-term potentiation (LTP) with resultant regulation of contextual fear memory and spatial learning. PTENα binds to CaMKII with its distinctive N terminus and resets CaMKII to an activatable state by dephosphorylating it at sites T305/306...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636947/assembly-secretory-pathway-trafficking-and-surface-delivery-of-kainate-receptors-is-regulated-by-neuronal-activity
#2
Ashley J Evans, Sonam Gurung, Kevin A Wilkinson, David J Stephens, Jeremy M Henley
Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636946/ptbp2-controls-an-alternative-splicing-network-required-for-cell-communication-during-spermatogenesis
#3
Molly M Hannigan, Leah L Zagore, Donny D Licatalosi
Alternative splicing has essential roles in development. Remarkably, spermatogenic cells express more alternatively spliced RNAs compared to most whole tissues; however, regulation of these RNAs remains unclear. Here, we characterize the alternative splicing landscape during spermatogenesis and reveal an essential function for the RNA-binding protein Ptbp2 in this highly regulated developmental program. We found that Ptbp2 controls a network of genes involved in cell adhesion, migration, and polarity, suggesting that splicing regulation by Ptbp2 is critical for germ cell communication with Sertoli cells (multifunctional somatic cells necessary for spermatogenesis)...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636945/pkn1-directs-polarized-rab21-vesicle-trafficking-via-rph3a-and-is-important-for-neutrophil-adhesion-and-ischemia-reperfusion-injury
#4
Qianying Yuan, Chunguang Ren, Wenwen Xu, Björn Petri, Jiasheng Zhang, Yong Zhang, Paul Kubes, Dianqing Wu, Wenwen Tang
Polarized vesicle transport plays an important role in cell polarization, but the mechanisms underlying this process and its role in innate immune responses are not well understood. Here, we describe a phosphorylation-regulated polarization mechanism that is important for neutrophil adhesion to endothelial cells during inflammatory responses. We show that the protein kinase PKN1 phosphorylates RPH3A, which enhances binding of RPH3A to guanosine triphosphate (GTP)-bound RAB21. These interactions are important for polarized localization of RAB21 and RPH3A in neutrophils, which leads to PIP5K1C90 polarization...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636944/transduction-of-repetitive-mechanical-stimuli-by-piezo1-and-piezo2-ion-channels
#5
Amanda H Lewis, Alisa F Cui, Malcolm F McDonald, Jörg Grandl
Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636943/opa1-isoforms-in-the-hierarchical-organization-of-mitochondrial-functions
#6
Valentina Del Dotto, Prashant Mishra, Sara Vidoni, Mario Fogazza, Alessandra Maresca, Leonardo Caporali, J Michael McCaffery, Martina Cappelletti, Enrico Baruffini, Guy Lenaers, David Chan, Michela Rugolo, Valerio Carelli, Claudia Zanna
OPA1 is a GTPase that controls mitochondrial fusion, cristae integrity, and mtDNA maintenance. In humans, eight isoforms are expressed as combinations of long and short forms, but it is unclear whether OPA1 functions are associated with specific isoforms and/or domains. To address this, we expressed each of the eight isoforms or different constructs of isoform 1 in Opa1(-/-) MEFs. We observed that any isoform could restore cristae structure, mtDNA abundance, and energetic efficiency independently of mitochondrial network morphology...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636942/extensive-proliferation-of-human-cancer-cells-with-ever-shorter-telomeres
#7
Rebecca A Dagg, Hilda A Pickett, Axel A Neumann, Christine E Napier, Jeremy D Henson, Erdahl T Teber, Jonathan W Arthur, C Patrick Reynolds, Jayne Murray, Michelle Haber, Alexander P Sobinoff, Loretta M S Lau, Roger R Reddel
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636941/highly-aggressive-metastatic-melanoma-cells-unable-to-maintain-telomere-length
#8
Nikenza Viceconte, Marie-Sophie Dheur, Eva Majerova, Christophe E Pierreux, Jean-François Baurain, Nicolas van Baren, Anabelle Decottignies
Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636940/hectd3-mediates-an-hsp90-dependent-degradation-pathway-for-protein-kinase-clients
#9
Zhaobo Li, Lihong Zhou, Chrisostomos Prodromou, Velibor Savic, Laurence H Pearl
Inhibition of the ATPase cycle of the HSP90 chaperone promotes ubiquitylation and proteasomal degradation of its client proteins, which include many oncogenic protein kinases. This provides the rationale for HSP90 inhibitors as cancer therapeutics. However, the mechanism by which HSP90 ATPase inhibition triggers ubiquitylation is not understood, and the E3 ubiquitin ligases involved are largely unknown. Using a siRNA screen, we have identified components of two independent degradation pathways for the HSP90 client kinase CRAF...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636939/the-super-enhancer-derived-alncrna-ec7-bloodlinc-potentiates-red-blood-cell-development-in%C3%A2-trans
#10
Juan R Alvarez-Dominguez, Marko Knoll, Austin A Gromatzky, Harvey F Lodish
Enhancer-derived RNAs are thought to act locally by contributing to their parent enhancer function. Whether large domains of clustered enhancers (super-enhancers) also produce cis-acting RNAs, however, remains unclear. Unlike typical enhancers, super-enhancers form large spans of robustly transcribed chromatin, amassing capped and polyadenylated RNAs that are sufficiently abundant to sustain trans functions. Here, we show that one such RNA, alncRNA-EC7/Bloodlinc, is transcribed from a super-enhancer of the erythroid membrane transporter SLC4A1/BAND3 but diffuses beyond this site...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636938/the-ldb1-complex-co-opts-ctcf-for-erythroid-lineage-specific-long-range-enhancer-interactions
#11
Jongjoo Lee, Ivan Krivega, Ryan K Dale, Ann Dean
Lineage-specific transcription factors are critical for long-range enhancer interactions, but direct or indirect contributions of architectural proteins such as CCCTC-binding factor (CTCF) to enhancer function remain less clear. The LDB1 complex mediates enhancer-gene interactions at the β-globin locus through LDB1 self-interaction. We find that an LDB1-bound enhancer upstream of carbonic anhydrase 2 (Car2) activates its expression by interacting directly with CTCF at the gene promoter. Both LDB1 and CTCF are required for enhancer-Car2 looping, and the domain of LDB1 contacted by CTCF is necessary to rescue Car2 transcription in LDB1-deficient cells...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636937/the-conserved-rna-binding-cyclophilin-rct1-regulates-small-rna-biogenesis-and-splicing-independent-of-heterochromatin-assembly
#12
An-Yun Chang, Stephane E Castel, Evan Ernst, Hyun Soo Kim, Robert A Martienssen
RNAi factors and their catalytic activities are essential for heterochromatin assembly in S. pombe. This has led to the idea that siRNAs can promote H3K9 methylation by recruiting the cryptic loci regulator complex (CLRC), also known as recombination in K complex (RIKC), to the nucleation site. The conserved RNA-binding protein Rct1 (AtCyp59/SIG-7) interacts with splicing factors and RNA polymerase II. Here we show that Rct1 promotes processing of pericentromeric transcripts into siRNAs via the RNA recognition motif...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636936/strong-tcr%C3%AE-%C3%AE-signaling-prohibits-thymic-development-of-il-17a-secreting-%C3%AE-%C3%AE-t-cells
#13
Nital Sumaria, Capucine L Grandjean, Bruno Silva-Santos, Daniel J Pennington
Despite a growing appreciation of γδ T cell contributions to numerous immune responses, the mechanisms that underpin their thymic development remain poorly understood. Here, using precursor/product relationships, we identify thymic stages in two distinct developmental pathways that generate γδ T cells pre-committed to subsequent secretion of either IL-17A or IFNγ. Importantly, this framework for tracking γδ T cell development has permitted definitive assessment of TCRγδ signal strength in commitment to γδ T cell effector fate; increased TCRγδ signal strength profoundly prohibited the development of all IL-17A-secreting γδ T cells, regardless of Vγ usage, but promoted the development of γδ progenitors along the IFNγ pathway...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636935/the-sensory-striatum-is-permanently-impaired-by-transient-developmental-deprivation
#14
Todd M Mowery, Kristina B Penikis, Stephen K Young, Christopher E Ferrer, Vibhakar C Kotak, Dan H Sanes
Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL), are commonly linked with processing deficits at or below the level of the auditory cortex (ACx). However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636934/the-tmao-producing-enzyme-flavin-containing-monooxygenase-3-regulates-obesity-and-the-beiging-of-white-adipose-tissue
#15
Rebecca C Schugar, Diana M Shih, Manya Warrier, Robert N Helsley, Amy Burrows, Daniel Ferguson, Amanda L Brown, Anthony D Gromovsky, Markus Heine, Arunachal Chatterjee, Lin Li, Xinmin S Li, Zeneng Wang, Belinda Willard, YongHong Meng, Hanjun Kim, Nam Che, Calvin Pan, Richard G Lee, Rosanne M Crooke, Mark J Graham, Richard E Morton, Carl D Langefeld, Swapan K Das, Lawrence L Rudel, Nizar Zein, Arthur J McCullough, Srinivasan Dasarathy, W H Wilson Tang, Bernadette O Erokwu, Chris A Flask, Markku Laakso, Mete Civelek, Sathyamangla V Naga Prasad, Joerg Heeren, Aldons J Lusis, Stanley L Hazen, J Mark Brown
Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636933/drosophila-neuropeptide-f-signaling-independently-regulates-feeding-and-sleep-wake-behavior
#16
Brian Y Chung, Jennifer Ro, Sabine A Hutter, Kylie M Miller, Lakshmi S Guduguntla, Shu Kondo, Scott D Pletcher
Proper regulation of sleep-wake behavior and feeding is essential for organismal health and survival. While previous studies have isolated discrete neural loci and substrates important for either sleep or feeding, how the brain is organized to coordinate both processes with respect to one another remains poorly understood. Here, we provide evidence that the Drosophila Neuropeptide F (NPF) network forms a critical component of both adult sleep and feeding regulation. Activation of NPF signaling in the brain promotes wakefulness and adult feeding, likely through its cognate receptor NPFR...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636932/ubiquitination-linked-phosphorylation-of-the-fanci-s-tq-cluster-contributes-to-activation-of-the-fanconi-anemia-i-d2-complex
#17
Ronald S Cheung, Maria Castella, Antonio Abeyta, Philip R Gafken, Nyka Tucker, Toshiyasu Taniguchi
Repair of interstrand crosslinks by the Fanconi anemia (FA) pathway requires both monoubiquitination and de-ubiquitination of the FANCI/FANCD2 (FANCI/D2) complex. In the standing model, the phosphorylation of six sites in the FANCI S/TQ cluster domain occurs upstream of, and promotes, FANCI/D2 monoubiquitination. We generated phospho-specific antibodies against three different S/TQ cluster sites (serines 556, 559, and 565) on human FANCI and found that, in contrast to the standing model, distinct FANCI sites were phosphorylated either predominantly upstream (ubiquitination independent; serine 556) or downstream (ubiquitination-linked; serines 559 and 565) of FANCI/D2 monoubiquitination...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636931/p53-prohibits-propagation-of-chromosome-segregation-errors-that-produce-structural-aneuploidies
#18
Mar Soto, Jonne A Raaijmakers, Bjorn Bakker, Diana C J Spierings, Peter M Lansdorp, Floris Foijer, René H Medema
The presence of an abnormal karyotype has been shown to be profoundly detrimental at the cellular and organismal levels but is an overt hallmark of cancer. Aneuploidy can lead to p53 activation and thereby prevents proliferation, but the exact trigger for p53 activation has remained controversial. Here, we have used a system to induce aneuploidy in untransformed human cells to explore how cells deal with different segregation errors. We show that p53 is activated only in a subset of the cells with altered chromosome content...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636930/a-tonoplast-p3b-atpase-mediates-fusion-of-two-types-of-vacuoles-in-petal-cells
#19
Marianna Faraco, Yanbang Li, Shuangjiang Li, Cornelis Spelt, Gian Pietro Di Sansebastiano, Lara Reale, Francesco Ferranti, Walter Verweij, Ronald Koes, Francesca M Quattrocchio
It is known that plant cells can contain multiple distinct vacuoles; however, the abundance of multivacuolar cells and the mechanisms underlying vacuolar differentiation and communication among different types of vacuoles remain unknown. PH1 and PH5 are tonoplast P-ATPases that form a heteromeric pump that hyper-acidifies the central vacuole (CV) of epidermal cells in petunia petals. Here, we show that the sorting of this pump and other vacuolar proteins to the CV involves transit through small vacuoles: vacuolinos...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28614725/integrative-analysis-of-prkag2-cardiomyopathy-ips-and-microtissue-models-identifies-ampk-as-a-regulator-of-metabolism-survival-and-fibrosis
#20
J Travis Hinson, Anant Chopra, Andre Lowe, Calvin C Sheng, Rajat M Gupta, Rajarajan Kuppusamy, John O'Sullivan, Glenn Rowe, Hiroko Wakimoto, Joshua Gorham, Michael A Burke, Kehan Zhang, Kiran Musunuru, Robert E Gerszten, Sean M Wu, Christopher S Chen, Jonathan G Seidman, Christine E Seidman
No abstract text is available yet for this article.
June 13, 2017: Cell Reports
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