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https://www.readbyqxmd.com/read/28545113/rac1-is-dispensable-for-oocyte-maturation-and-female-fertility-in-vivo
#1
Jian-Xiu Hao, Tie-Gang Meng, Li-Hua Fan, Yuan-Qing Yao
Oocyte maturation, the important process to produce female haploid gamete, accompanies with polarity establishment and highly asymmetric cell division to emit minor polar body within little cytoplasm. Microfilaments play central roles in polarity establishment and asymmetric cell division. Several actin regulators like WASP protein family as well as small GTPases function in microfilament dynamics, involving the process. Rac1, one member of RhoGTPases, has been reported to regulate the polarity and asymmetric cell division in mouse oocytes in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28544529/excess-cholesterol-inhibits-glucose-stimulated-fusion-pore-dynamics-in-insulin-exocytosis
#2
Yingke Xu, Derek K Toomre, Jonathan S Bogan, Mingming Hao
Type 2 diabetes is caused by defects in both insulin sensitivity and insulin secretion. Glucose triggers insulin secretion by causing exocytosis of insulin granules from pancreatic β-cells. High circulating cholesterol levels and a diminished capacity of serum to remove cholesterol from β-cells are observed in diabetic individuals. Both of these effects can lead to cholesterol accumulation in β-cells and contribute to β-cell dysfunction. However, the molecular mechanisms by which cholesterol accumulation impairs β-cell function remain largely unknown...
May 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28541439/the-evolutionary-landscape-of-dbl-like-rhogef-families-adapting-eukaryotic-cells-to-environmental-signals
#3
Philippe Fort, Anne Blangy
The dynamics of cell morphology in eukaryotes is largely controlled by small GTPases of the Rho family. Rho GTPases are activated by Guanine nucleotide Exchange Factors (RhoGEFs), of which Diffuse B-cell Lymphoma (Dbl)-like members form the largest family. Here we surveyed Dbl-like sequences from 175 eukaryotic genomes and illuminate how the Dbl family evolved in all eukaryotic supergroups. By combining probabilistic phylogenetic approaches and functional domain analysis, we show that the human Dbl-like family is made of 71 members, structured into 20 subfamilies...
May 25, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28539409/spatial-analysis-of-cdc42-activity-reveals-a-role-for-plasma-membrane-associated-cdc42-in-centrosome-regulation
#4
Kari A Herrington, Andrew L Trinh, Carolyn Dang, Ellen O'Shaughnessy, Klaus M Hahn, Enrico Gratton, Michelle A Digman, Christine Sütterlin
The ability of the small GTPase Cdc42 to regulate diverse cellular processes depends on tight spatial control of its activity. Cdc42 function is best understood at the plasma membrane (PM), where it regulates cytoskeletal organization and cell polarization. Active Cdc42 has also been detected at the Golgi, but its role and regulation at this organelle is only partially understood. Here we analyze the spatial distribution of Cdc42 activity by monitoring the dynamics of the Cdc42 FLARE biosensor using the phasor approach to FLIM-FRET...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539387/gop-1-helping-phagosomes-pass-the-acid-test
#5
Lynda M Stuart, Adam Lacy-Hulbert
Phagosomes form during engulfment of large particles and become increasingly acidic and proteolytic, ultimately fusing with lysosomes, in a process termed "phagosome maturation." In this issue, Yin et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610001) identify GOP-1 as essential for the maturation of phagosomes containing apoptotic cells, through recruitment of the Rab GTPase UNC108.
May 24, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#6
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28536001/membrane-shaping-by-actin-and-myosin-during-regulated-exocytosis
#7
REVIEW
Andreas Papadopulos
The cortical actin network in neurosecretory cells is a dense mesh of actin filaments underlying the plasma membrane. Interaction of actomyosin with vesicular membranes or the plasma membrane is vital for tethering, retention, transport as well as fusion and fission of exo- and endocytic membrane structures. During regulated exocytosis the cortical actin network undergoes dramatic changes in morphology to accommodate vesicle docking, fusion and replenishment. Most of these processes involve plasma membrane Phosphoinositides (PIP) and investigating the interactions between the actin cortex and secretory structures has become a hotbed for research in recent years...
May 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28532301/heterotrimeric-g-protein-regulatory-circuits-in-plants-conserved-and-novel-mechanisms
#8
Sona Pandey
Article Addendum Efficient activation and deactivation of Gα protein is critical for the regulation of heterotrimeric G-protein mediated signaling pathways. While the core G-protein components and their activation/deactivation chemistries are broadly conserved throughout the eukaryotic evolution, their regulatory mechanisms seem to have been rewired in plants to meet specific needs. Plants such as Arabidopsis, which have a limited number of G-protein components and their regulators, offer a unique opportunity to dissect the mechanistic details of distinct signaling pathways...
May 22, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28528353/adrenomedullin-ameliorates-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro-and-in-vivo-through-modulation-of-rho-gtpases
#9
Nan Dong, Lixia Meng, Ruqun Xue, Meng Yu, Zhonghua Zhao, Xueguang Liu
PURPOSE: Podocyte injury is a key event in proteinuric kidney disease and eventually glomerular scarring. While adrenomedullin (AM), a potent vasodilatory peptide, has been reported to confer renoprotection in several experimental models of kidney diseases, its effect on injured podocytes and the related mechanism is still largely unknown. METHODS: Employing Western blotting analysis, immunoprecipitation and immunofluorescence, we investigated the effects of AM on the expressions of podocyte cytoskeletal proteins and Rho-family small GTPases (Rho GTPases) in puromycin aminonucleoside (PAN)-induced podocyte injury, both in cultured podocytes and in PAN nephrosis rats...
May 20, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28527895/suppression-of-pmrab11-inhibits-yhv-infection-in-penaeus-monodon
#10
Akechai Kongprajug, Sakol Panyim, Chalermporn Ongvarrasopone
Yellow head virus (YHV) is one of the most serious pathogens that causes worldwide shrimp production loss. It enters the cells via clathrin-mediated endocytosis and utilizes small GTPase Rab proteins such as PmRab5 and PmRab7 for intracellular trafficking. In this study, molecular cloning and functional analysis of Rab11 during YHV infection were investigated. PmRab11 cDNA was cloned by Rapid amplification of cDNA ends (RACEs). It contained two forms of sizes 1200 and 1050 bp distinct at the 5' UTR. The coding region of PmRab11 was 645 bp, encoding 214 amino acids...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28527631/the-thiol-switch-c684-in-mitofusin-2-mediates-redox-induced-alterations-of-mitochondrial-shape-and-respiration
#11
Osamah Thaher, Christina Wolf, Partha Narayan Dey, Alireza Pouya, Verena Wüllner, Stefan Tenzer, Axel Methner
Mitofusin-2 (MFN2) is a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. MFN2 also plays a role in mitochondrial fusion induced by changes in the intracellular redox state. Adding oxidized glutathione (GSSG), the core cellular stress indicator, to mitochondrial preparations stimulates mitochondrial fusion by inducing disulphide bond-mediated oligomer formation of MFN2 and its homolog MFN1 which involve cysteine 684 (C684) of MFN2. Mitochondrial hyperfusion represents an adaptive stress response that confers transient protection by increasing mitochondrial ATP production but how this depends on the thiol switch C684 in MFN2 has not been investigated...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28527113/mutant-p53-promotes-cell-spreading-and-migration-via-arhgap44
#12
Jinjin Xu, Jian Jiao, Wei Xu, Lei Ji, Dongjie Jiang, Shaofang Xie, Syeda Kubra, Xiaotao Li, Junjiang Fu, Jianru Xiao, Bianhong Zhang
The tumor suppressor p53 protein is either lost or mutated in about half of all human cancers. Loss of p53 function is well known to influence cell spreading, migration and invasion. While expression of mutant p53 is not equivalent to p53 loss, mutant p53 can acquire new functions to drive cell spreading and migration via different mechanisms. In our study, we found that mutant p53 significantly increased cell spreading and migration when comparing with p53-null cells. RNA-Seq analysis suggested that Rho GTPase activating protein 44 (ARHGAP44) is a new target of mutant p53, which suppressed ARHGAP44 transcription...
May 16, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28525892/rasal1-is-a-potent-regulator-of-hepatic-stellate-cell-activity-and-liver-fibrosis
#13
Akemi Takata, Motoyuki Otsuka, Takahiro Kishikawa, Mari Yamagami, Rei Ishibashi, Kazuma Sekiba, Tatsunori Suzuki, Motoko Ohno, Yui Yamashita, Takaya Abe, Ryota Masuzaki, Tsuneo Ikenoue, Kazuhiko Koike
Liver fibrosis, leading to cirrhosis and liver failure, can occur after chronic liver injury. The transition of hepatic stellate cells (HSCs) from quiescent cells into proliferative and fibrogenic cells is a central event in liver fibrosis. Here, we show that RAS protein activator like-1 (RASAL1), a RAS-GTPase-activating protein, which switches off RAS activity, is significantly decreased during HSC activation, and that HSC activation can be antagonized by forced expression of the RASAL1 protein. We demonstrate that RASAL1 suppresses HSC proliferation by regulating the Ras-MAPK pathway, and that RASAL1 suppresses HSC fibrogenic activity by regulating the PKA-LKB1-AMPK-SRF pathway by interacting with angiotensin II receptor, type 1...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525545/gene-co-expression-network-analysis-for-identifying-modules-and-functionally-enriched-pathways-in-sca2
#14
Lance T Pflieger, Warunee Dansithong, Sharan Paul, Daniel Scoles, Karla P Figueroa, Pratap Meera, Thomas S Otis, Julio C Facelli, Stefan M Pulst
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The repeat resides in an encoded region of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein. We evaluated temporal cerebellar expression profiles by RNA sequencing of ATXN2Q127 mice vs wildtype littermates. ATXN2Q127 mice are characterized by a progressive motor phenotype onset, and have progressive cerebellar molecular and neurophysiological (Purkinje cell firing frequency) phenotypes...
May 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28525271/electron-spin-relaxation-and-biochemical-characterization-of-the-hydrogenase-maturase-hydf-insights-into-2fe-2s-and-4fe-4s-cluster-communication-and-hydrogenase-activation
#15
Eric M Shepard, Amanda S Byer, Priyanka Aggarwal, Jeremiah N Betz, Anna G Scott, Krista Shisler, Robert J Usselman, Gareth R Eaton, Sandra S Eaton, Joan B Broderick
Nature utilizes [FeFe]-hydrogenase enzymes to catalyze the interconversion between H2 and protons and electrons. Catalysis occurs at the H-cluster, a carbon monoxide, cyanide, and dithiomethylamine-coordinated 2Fe subcluster bridged via a cysteine to a [4Fe-4S] cluster. Biosynthesis of this unique metallocofactor is accomplished by three maturase enzymes denoted HydE, HydF, and HydG. HydE and HydG belong to the radical S-adenosylmethionine superfamily of enzymes and synthesize the nonprotein ligands of the H-cluster...
May 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28524846/concerted-regulation-of-retinal-pigment-epithelium-basement-membrane-and-barrier-function-by-angiocrine-factors
#16
Ignacio Benedicto, Guillermo L Lehmann, Michael Ginsberg, Daniel J Nolan, Rohan Bareja, Olivier Elemento, Zelda Salfati, Nazia M Alam, Glen T Prusky, Pierre Llanos, Sina Y Rabbany, Arvydas Maminishkis, Sheldon S Miller, Shahin Rafii, Enrique Rodriguez-Boulan
The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period...
May 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28524815/anchoring-high-concentrations-of-syngap-at-postsynaptic-densities-via-liquid-liquid-phase-separation
#17
Menglong Zeng, Guanhua Bai, Mingjie Zhang
SynGAP, encoded by SYNGAP1, is a Ras/Rap GTPase activator specifically expressed in the nervous systems. SynGAP is one of the most abundant proteins in the postsynaptic densities (PSDs) of excitatory synapses and acts as a critical synaptic activity brake by tuning down synaptic GTPase activities. Mutations of SYNGAP1 have been frequently linked to brain disorders including intellectual disability, autisms, and seizure. SynGAP has been shown to undergo fast dispersions from synapses in response to stimulations, a strategy that neurons use to control the specific activities of the enzyme within the tiny, semi-open compartments in dendritic spines...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28524754/arf-gtpase-interplay-with-rho-gtpases-in-regulation-of-the-actin-cytoskeleton
#18
Vikash Singh, Anthony C Davidson, Peter J Hume, Daniel Humphreys, Vassilis Koronakis
The Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28523344/role-of-g3bp1-in-glucocorticoid-receptor-mediated-microrna-15b-and-microrna-23a-biogenesis-in-endothelial-cells
#19
Hoi-Hin Kwok, Po-Ying Poon, Kylie Hin-Man Mak, Lin-Yao Zhang, Pei Liu, Huoming Zhang, Nai-Ki Mak, Patrick Ying-Kit Yue, Ricky Ngok-Shun Wong
MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells...
May 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28523202/identification-of-a-novel-alternatively-spliced-form-of-inflammatory-regulator-swap-70-like-adapter-of-t-cells
#20
Marie Hashimoto, Jun-Ichi Nagao, Shojiro Ikezaki, Sonoko Tasaki, Ken-Ichi Arita-Morioka, Yuka Narita, Tamaki Cho, Kenji Yuasa, Amnon Altman, Yoshihiko Tanaka
Activation of naive CD4(+) T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4(+) T cell inflammatory responses by controlling Ca(2+)/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2-7 of the Def6 gene...
2017: International Journal of Inflammation
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