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https://www.readbyqxmd.com/read/29244804/conditional-knockout-mice-for-the-distal-appendage-protein-cep164-reveal-its-essential-roles-in-airway-multiciliated-cell-differentiation
#1
Saul S Siller, Himanshu Sharma, Shuai Li, June Yang, Yong Zhang, Michael J Holtzman, Wipawee Winuthayanon, Holly Colognato, Bernadette C Holdener, Feng-Qian Li, Ken-Ichi Takemaru
Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide the motive force for mucociliary clearance, cerebrospinal fluid circulation, and ovum transport. Despite their clear importance to human biology and health, the molecular mechanisms underlying multiciliated cell differentiation are poorly understood. Prior studies implicate the distal appendage/transition fiber protein CEP164 as a central regulator of primary ciliogenesis; however, its role in multiciliogenesis remains unknown...
December 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29244730/isolation-and-characterization-of-ftsz-genes-in-cassava
#2
Meng-Ting Geng, Yi Min, Yuan Yao, Xia Chen, Jie Fan, Shuai Yuan, Lei Wang, Chong Sun, Fan Zhang, Lu Shang, Yun-Lin Wang, Rui-Mei Li, Shao-Ping Fu, Rui-Jun Duan, Jiao Liu, Xin-Wen Hu, Jian-Chun Guo
The filamenting temperature-sensitive Z proteins (FtsZs) play an important role in plastid division. In this study, three FtsZ genes were isolated from the cassava genome, and named MeFtsZ1, MeFtsZ2-1, and MeFtsZ2-2, respectively. Based on phylogeny, the MeFtsZs were classified into two groups (FtsZ1 and FtsZ2). MeFtsZ1 with a putative signal peptide at N-terminal, has six exons, and is classed to FtsZ1 clade. MeFtsZ2-1 and MeFtsZ2-2 without a putative signal peptide, have seven exons, and are classed to FtsZ2 clade...
December 15, 2017: Genes
https://www.readbyqxmd.com/read/29242851/in-depth-ptdins-3-4-5-p3-signalosome-analysis-identifies-dapp1-as-a-negative-regulator-of-gpvi-driven-platelet-function
#3
Tom N Durrant, James L Hutchinson, Kate J Heesom, Karen E Anderson, Len R Stephens, Phillip T Hawkins, Aaron J Marshall, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI3K) isoforms play important roles in platelet priming, activation, and stable thrombus formation. Class I PI3Ks predominantly regulate cell function through their catalytic product, the signaling phospholipid phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], which coordinates the localization and/or activity of a diverse range of binding proteins. Notably, the complete repertoire of these class I PI3K effectors in platelets remains unknown, limiting mechanistic understanding of class I PI3K-mediated control of platelet function...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29241666/identification-of-human-circadian-genes-based-on-time-course-gene-expression-profiles-by-using-a-deep-learning-method
#4
Peng Cui, Tingyan Zhong, Zhuo Wang, Tao Wang, Hongyu Zhao, Chenglin Liu, Hui Lu
Circadian genes express periodically in an approximate 24-h period and the identification and study of these genes can provide deep understanding of the circadian control which plays significant roles in human health. Although many circadian gene identification algorithms have been developed, large numbers of false positives and low coverage are still major problems in this field. In this study we constructed a novel computational framework for circadian gene identification using deep neural networks (DNN) a deep learning algorithm which can represent the raw form of data patterns without imposing assumptions on the expression distribution...
December 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29241551/sorting-tubules-regulate-blood-brain-barrier-transcytosis
#5
Roberto Villaseñor, Michael Schilling, Janani Sundaresan, Yves Lutz, Ludovic Collin
Transcytosis across the blood-brain barrier (BBB) regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs) remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29240824/high-abundance-of-arfgap1-found-in-the-mossy-fibers-in-hilus-of-the-dentate-gyrus-region-of-the-mouse-brain
#6
Sergiy Chornyy, Anna Parnis, Michael Shmoish, Dan Cassel
The Arf GTPase-activating protein ArfGAP1 and its brain-specific isoform ArfGAP1B play an important role in neurotransmission. Here we analyzed the distribution of ArfGAP1 in the mouse brain. We found high levels of ArfGAP1 in the mouse dentate gyrus where it displayed especially elevated level in the polymorph layer (hilus). Importantly, the ArfGAP1 signal follows the pathway of the granular cell axons so-called mossy fibers which extend from the dentate gyrus to CA3 via stratum lucidum and partially stratum oriens...
2017: PloS One
https://www.readbyqxmd.com/read/29239724/sirt2-and-lysine-fatty-acylation-regulate-the-transforming-activity-of-k-ras4a
#7
Hui Jing, Xiaoyu Zhang, Stephanie A Wisner, Xiao Chen, Nicole A Spiegelman, Maurine E Linder, Hening Lin
Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a...
December 14, 2017: ELife
https://www.readbyqxmd.com/read/29239692/consequences-of-rab-gtpase-dysfunction-in-genetic-or-acquired-human-diseases
#8
Marcellus J Banworth, Guangpu Li
Rab GTPases are important regulators of intracellular membrane trafficking in eukaryotes. Both activating and inactivating mutations in Rab genes have been identified and implicated in human diseases ranging from neurological disorders to cancer. In addition, altered Rab expression is often associated with disease prognosis. As such, the study of diseases associated with Rabs or Rab-interacting proteins has shed light on the important role of intracellular membrane trafficking in disease etiology. In this review, we cover recent advances in the field with an emphasis on cellular mechanisms...
December 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/29239216/protein-depalmitoylases
#9
Sang Joon Won, Melanie Cheung See Kit, Brent R Martin
Protein depalmitoylation describes the removal of thioester-linked long chain fatty acids from cysteine residues in proteins. For many S-palmitoylated proteins, this process is promoted by acyl protein thioesterase enzymes, which catalyze thioester hydrolysis to solubilize and displace substrate proteins from membranes. The closely related enzymes acyl protein thioesterase 1 (APT1; LYPLA1) and acyl protein thioesterase 2 (APT2; LYPLA2) were initially identified from biochemical assays as G protein depalmitoylases, yet later were shown to accept a number of S-palmitoylated protein and phospholipid substrates...
December 14, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29238204/low-expression-of-dab2ip-predicts-an-unfavorable-prognosis-in-human-bladder-carcinoma
#10
Linfeng Zheng, Kaiyan Chen, Liang Zhu, Dan Su, Guoping Cheng
The DOC-2/DAB2 interactive protein (DAB2IP) is a novel member of the Ras GTPase-activating protein family, and its downregulation is an unfavorable prognostic factor in several human malignancies. In this study, we retrospectively analyzed clinicopathological features, outcomes, and DAB2IP expression in 77 patients with urothelial carcinoma of the bladder (UCB). Expression of DAB2IP and p-STAT3 was examined in tumors and in matched adjacent non-cancerous tissues, using immunohistochemistry. We found a marked reduction in the expression of DAB2IP in UCB specimens, which was significantly associated with advanced pathological stage (P=0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29237821/sequential-actions-of-phosphatidylinositol-phosphates-regulate-phagosome-lysosome-fusion
#11
Andreas Jeschke, Albert Haas
Phagosomes mature into phagolysosomes by sequential fusion with early endosomes, late endosomes, and lysosomes. Phagosome-with-lysosome fusion (PLF) results in the delivery of lysosomal hydrolases into phagosomes and in digestion of the cargo. The machinery that drives PLF has been little investigated. Using a cell-free system, we recently identified the phosphoinositide lipids (PIPs) phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 4-phosphate [PI(4)P] as regulators of PLF. We now report the identification and the PIP requirements of four distinct sub-reactions of PLF...
December 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29237817/an-arf6-and-caveolae-dependent-pathway-links-hemidesmosome-remodeling-and-mechanoresponse
#12
Naël Osmani, Julien Pontabry, Jordi Comelles, Nina Fekonja, Jacky G Goetz, Daniel Riveline, Elisabeth Georges-Labouesse, Michel Labouesse
Hemidesmosomes (HDs) are epithelial-specific cell-matrix adhesions, which stably anchor the intracellular keratin network to the extracellular matrix. Although their main role is to protect the epithelial sheet from external mechanical strain, how HDs respond to mechanical stress remains poorly understood. Here we identify a pathway essential for HD remodeling, and outline its role with respect to α6β4 integrin recycling. We find that α6β4 integrin chains localize to the plasma membrane, caveolae and Arf6+ endocytic compartments...
December 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29237056/the-plant-membrane-surrounding-powdery-mildew-haustoria-shares-properties-with-the-endoplasmic-reticulum-membrane
#13
Mark Kwaaitaal, Mads Eggert Nielsen, Henrik Böhlenius, Hans Thordal-Christensen
Many filamentous plant pathogens place specialized feeding structures, called haustoria, inside living host cells. As haustoria grow, they are believed to manipulate plant cells to generate a specialized, still enigmatic extrahaustorial membrane (EHM) around them. Here, we focused on revealing properties of the EHM. With the help of membrane-specific dyes and transient expression of membrane-associated proteins fused to fluorescent tags, we studied the nature of the EHM generated by barley leaf epidermal cells around powdery mildew haustoria...
December 9, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29236694/dynamics-of-phosphoinositide-conversion-in-clathrin-mediated-endocytic-traffic
#14
Kangmin He, Robert Marsland Iii, Srigokul Upadhyayula, Eli Song, Song Dang, Benjamin R Capraro, Weiming Wang, Wesley Skillern, Raphael Gaudin, Minghe Ma, Tom Kirchhausen
Vesicular carriers transport proteins and lipids from one organelle to another, recognizing specific identifiers for the donor and acceptor membranes. Two important identifiers are phosphoinositides and GTP-bound GTPases, which provide well-defined but mutable labels. Phosphatidylinositol and its phosphorylated derivatives are present on the cytosolic faces of most cellular membranes. Reversible phosphorylation of its headgroup produces seven distinct phosphoinositides. In endocytic traffic, phosphatidylinositol-4,5-biphosphate marks the plasma membrane, and phosphatidylinositol-3-phosphate and phosphatidylinositol-4-phosphate mark distinct endosomal compartments...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29236692/mechanisms-of-mtorc1-activation-by-rheb-and-inhibition-by-pras40
#15
Haijuan Yang, Xiaolu Jiang, Buren Li, Hyo J Yang, Meredith Miller, Angela Yang, Ankita Dhar, Nikola P Pavletich
The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29235861/kras-switch-mutants-d33e-and-a59g-crystallize-in-the-state-1-conformation
#16
Jia Lu, Asim Bera, Sudershan R Gondi, Kenneth Dale Westover
KRAS switch loop movements play a crucial role in regulating RAS signaling and alteration in these sensitive dynamics are a principal mechanism through which disease-associated RAS mutations lead to aberrant RAS activation. Prior studies suggest that despite high sequence similarity, the switches in KRAS are more dynamic than HRAS. We solved x-ray crystal structures of the rare tumorigenic KRAS mutants KRASD33E, in switch 1 (SW1), and KRASA59G, in switch 2 (SW2), bound to GDP and found these adopt nearly identical, open SW1 conformations as well as altered SW2 conformations...
December 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/29235562/targeting-the-raf-kinases-in-human-cancer-the-raf-dimer-dilemma
#17
David E Durrant, Deborah K Morrison
The Raf protein kinases are key intermediates in cellular signal transduction, functioning as direct effectors of the Ras GTPases and as the initiating kinases in the ERK cascade. In human cancer, Raf activity is frequently dysregulated due to mutations in the Raf family member B-Raf or to alterations in upstream Raf regulators, including Ras and receptor tyrosine kinases. First-generation Raf inhibitors, such as vemurafenib and dabrafenib, have yielded dramatic responses in malignant melanomas containing B-Raf mutations; however, their overall usefulness has been limited by both intrinsic and acquired drug resistance...
December 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29235178/the-gp130-cytokine-il-11-regulates-engraftment-of-vav1-hematopoietic-stem-and-progenitor-cells-in-lethally-irradiated-recipients
#18
Serena De Vita, Yanhua Li, Chad E Harris, Meaghan K McGuinness, Clement Ma, David A Williams
During bone marrow transplantation (BMT), hematopoietic stem and progenitor cells (HSPCs) respond to signals from the hematopoietic microenvironment (HM) by coordinately activating molecular pathways through Rho GTPases, including Rac. We have previously shown that deletion of Vav1, a hematopoietic-specific activator of Rac, compromises engraftment of transplanted adult HSPCs without affecting steady-state hematopoiesis in adult animals. Here, we show that Vav1-/- fetal HSPCs can appropriately seed hematopoietic tissues during ontogeny but cannot engraft into lethally irradiated recipients...
December 13, 2017: Stem Cells
https://www.readbyqxmd.com/read/29235176/roles-of-elusive-translational-gtpases-come-to-light-and-inform-on-the-process-of-ribosome-biogenesis-in-bacteria
#19
REVIEW
Michelle R Gibbs, Kurt Fredrick
Protein synthesis relies on several translational GTPases (trGTPases), related proteins that couple the hydrolysis of GTP to specific molecular events on the ribosome. Most bacterial trGTPases, including IF2, EF-Tu, EF-G, and RF3, play well-known roles in translation. The cellular functions of LepA (also termed EF4) and BipA (also termed TypA), on the other hand, have remained enigmatic. Recent studies provide compelling in vivo evidence that LepA and BipA function in biogenesis of the 30S and 50S subunit, respectively...
December 13, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29234285/a-microarray-study-of-carpet-shell-clam-ruditapes-decussatus-shows-common-and-organ-specific-growth-related-gene-expression-differences-in-gills-and-digestive-gland
#20
Carlos Saavedra, Massimo Milan, Ricardo B Leite, David Cordero, Tomaso Patarnello, M Leonor Cancela, Luca Bargelloni
Growth rate is one of the most important traits from the point of view of individual fitness and commercial production in mollusks, but its molecular and physiological basis is poorly known. We have studied differential gene expression related to differences in growth rate in adult individuals of the commercial marine clam Ruditapes decussatus. Gene expression in the gills and the digestive gland was analyzed in 5 fast-growing and five slow-growing animals by means of an oligonucleotide microarray containing 14,003 probes...
2017: Frontiers in Physiology
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