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https://www.readbyqxmd.com/read/28935466/morphomechanical-and-structural-changes-induced-by-rock-inhibitor-in-breast-cancer-cells
#1
Mariafrancesca Cascione, Valeria De Matteis, Chiara Cristina Toma, Paolo Pellegrino, Stefano Leporatti, Rosaria Rinaldi
The EMT phenomenon is based on tumour progression. The cells lose their physiologic phenotype and assumed a mesenchymal phenotype characterized by an increased migratory capacity, invasiveness and high resistance to apoptosis. In this process, RHO family regulates the activation or suppression of ROCK (Rho-associated coiled-coil containing protein kinase) which in turn regulates the cytoskeleton dynamics. However, while the biochemical mechanisms are widely investigated, a comprehensive and careful estimation of biomechanical changes has not been extensively addressed...
September 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28924375/lncrna-afap1-as-functions-as-a-competing-endogenous-rna-to-regulate-rap1b-expression-by-sponging-mir-181a-in-the-hscr
#2
Guanglin Chen, Lei Peng, Zhongxian Zhu, Chunxia Du, Ziyang Shen, Rujin Zang, Yang Su, Yankai Xia, Weibing Tang
Background: Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in a broad spectrum of cellular processes including development and disease. Despite the known engagement of the AFAP1-AS in several human diseases, its biological function in Hirschsprung disease (HSCR) remains elusive. Methods: We used qRT-PCR to detect the relative expression of AFAP1-AS in 64 HSCR bowel tissues and matched normal intestinal tissues. The effects of AFAP1-AS on cell proliferation, migration, cell cycle, apoptosis and cytoskeletal organization were evaluated using CCK-8, transwell assay, flow cytometer analysis and immunofluorescence, in 293T and SH-SY5Y cell lines, respectively...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28923883/microtubules-associated-rac-regulation-of-endothelial-barrier-a-role-of-asef-in-acute-lung-injury
#3
Pratap Karki, Anna A Birukova
The endothelial barrier function regulated by the cytoskeletal reorganizations has been implicated in the pathogenesis of multiple lung diseases including asthma, sepsis, edema, and acute respiratory distress syndrome. The extensive studies have established that activation of small GTPase Rac is a key mechanism in endothelial barrier protection but the role of microtubules-associated Rac in the endothelial functions remains poorly understood. With the emerging evidences that microtubules disassembly also plays a critical role in actin cytoskeleton remodeling leading to endothelial permeability, the knowledge on microtubules-mediated regulation of endothelial barrier is imperative to better understand the etiology of lung injuries as well as to develop novel therapeutics against these disorders...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28918435/infant-avoidance-training-alters-cellular-activation-patterns-in-prefronto-limbic-circuits-during-adult-avoidance-learning-ii-cellular-imaging-of-neurons-expressing-the-activity-regulated-cytoskeleton-associated-protein-arc-arg3-1
#4
Nicole Gröger, Anja Mannewitz, Jörg Bock, Susann Becker, Katja Guttmann, Gerd Poeggel, Katharina Braun
Positive and negative feedback learning is essential to optimize behavioral performance. We used the two-way active avoidance (TWA) task as an experimental paradigm for negative feedback learning with the aim to test the hypothesis that neuronal ensembles activate the activity-regulated cytoskeletal (Arc/Arg3.1) protein during different phases of avoidance learning and during retrieval. A variety of studies in humans and other animals revealed that the ability of aversive feedback learning emerges postnatally...
September 16, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28911825/paving-the-rho-in-cancer-metastasis-rho-gtpases-and-beyond
#5
REVIEW
Sepp Jansen, Reinoud Gosens, Thomas Wieland, Martina Schmidt
Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28904993/abnormalities-of-signal-transduction-networks-in-chronic-schizophrenia
#6
Jennifer L McGuire, Erica A Depasquale, Adam J Funk, Sinead M O'Donnovan, Kathryn Hasselfeld, Shruti Marwaha, John H Hammond, Vahram Hartounian, James H Meador-Woodruff, Jarek Meller, Robert E McCullumsmith
Schizophrenia is a serious neuropsychiatric disorder characterized by disruptions of brain cell metabolism, microstructure, and neurotransmission. All of these processes require coordination of multiple kinase-mediated signaling events. We hypothesize that imbalances in kinase activity propagate through an interconnected network of intracellular signaling with potential to simultaneously contribute to many or all of the observed deficits in schizophrenia. We established a workflow distinguishing schizophrenia-altered kinases in anterior cingulate cortex using a previously published kinome array data set...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28900113/abnormalities-of-signal-transduction-networks-in-chronic-schizophrenia
#7
Jennifer L McGuire, Erica A Depasquale, Adam J Funk, Sinead M O'Donnovan, Kathryn Hasselfeld, Shruti Marwaha, John H Hammond, Vahram Hartounian, James H Meador-Woodruff, Jarek Meller, Robert E McCullumsmith
Schizophrenia is a serious neuropsychiatric disorder characterized by disruptions of brain cell metabolism, microstructure, and neurotransmission. All of these processes require coordination of multiple kinase-mediated signaling events. We hypothesize that imbalances in kinase activity propagate through an interconnected network of intracellular signaling with potential to simultaneously contribute to many or all of the observed deficits in schizophrenia. We established a workflow distinguishing schizophrenia-altered kinases in anterior cingulate cortex using a previously published kinome array data set...
September 12, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28894085/p190rhogap-proteins-contain-pseudogtpase-domains
#8
Amy L Stiegler, Titus J Boggon
The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the 'middle domain', previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support defects in nucleotide-binding activity...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28892050/carcinoembryonic-antigen-related-cell-adhesion-molecule-6-ceacam6-promotes-egf-receptor-signaling-of-oral-squamous-cell-carcinoma-metastasis-via-the-complex-n-glycosylation
#9
W-F Chiang, T-M Cheng, C-C Chang, S-H Pan, C A Changou, T-H Chang, K-H Lee, S-Y Wu, Y-F Chen, K-H Chuang, D-B Shieh, Y-L Chen, C-C Tu, W-L Tsui, M-H Wu
Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28887403/the-functions-of-reelin-in-membrane-trafficking-and-cytoskeletal-dynamics-implications-for-neuronal-migration-polarization-and-differentiation
#10
REVIEW
Jessica Santana, María-Paz Marzolo
Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1)...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28882898/switch-i-dependent-allosteric-signaling-in-a-g-protein-chaperone-b12-enzyme-complex
#11
Gregory C Campanello, Michael Lofgren, Adam L Yokom, Daniel R Southworth, Ruma Banerjee
G-proteins regulate various processes ranging from DNA replication and protein synthesis to cytoskeletal dynamics and cofactor assimilation, and serve as models for uncovering strategies deployed for allosteric signal transduction. MeaB is a multifunctional G-protein chaperone, which gates loading of the active 5'-deoxyadenosylcobalamin cofactor onto methylmalonyl-CoA mutase (MCM) and precludes loading of inactive cofactor forms. MeaB also safeguards MCM, which uses radical chemistry, against inactivation and rescues MCM inactivated during catalytic turnover by using the GTP-binding energy to offload inactive cofactor...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28882678/rna-interference-mediated-knockdown-of-sirt1-and-or-sirt2-in-melanoma-identification-of-downstream-targets-by-large-scale-proteomics-analysis
#12
Melissa J Wilking-Busch, Mary A Ndiaye, Xiaoqi Liu, Nihal Ahmad
Melanoma is the most notorious and fatal of all skin cancers and the existing treatment options have not been proven to effectively manage this neoplasm, especially the metastatic disease. Sirtuin (SIRT) proteins have been shown to be differentially expressed in melanoma. We have shown that SIRTs 1 and 2 were overexpressed in melanoma and inhibition of SIRT1 imparts anti-proliferative responses in human melanoma cells. To elucidate the impact of SIRT 1 and/or 2 in melanoma, we created stable knockdowns of SIRTs 1, 2, and their combination using shRNA mediated RNA interference in A375 human melanoma cells...
September 4, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28881620/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#13
Ruolan Dong, Danli Hu, Yan Yang, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880939/arf6-mediates-nephrin-tyrosine-phosphorylation-induced-podocyte-cellular-dynamics
#14
Jamie S Lin, Jin Seok Jeon, Qingfeng Fan, Hetty N Wong, Matthew B Palmer, Lawrence B Holzman
ADP-ribosylation factor 6 (ARF6) is a small GTPase necessary for regulating cellular structure, motility, and vesicle trafficking. In several cellular systems, ARF6 was shown to regulate actin dynamics in coordination with Rac1, a Rho small GTPase. We examined the function of ARF6 in the kidney podocyte because Rac1 was implicated in kidney diseases involving this cell. We found that ARF6 expression was enriched in human podocytes and that it modulated podocyte cytoskeletal dynamics through a functional interaction with nephrin, an intercellular junction protein necessary for podocyte injury-induced signaling requiring activation by tyrosine phosphorylation of its cytoplasmic domain...
2017: PloS One
https://www.readbyqxmd.com/read/28880478/role-of-g-proteins-in-islet-function-in-health-and-diabetes
#15
REVIEW
Anjaneyulu Kowluru
Glucose-stimulated insulin secretion (GSIS) involves interplay between metabolic and cationic events. Seminal contributions from multiple laboratories affirm essential roles for small G-proteins (Rac1, Cdc42, Arf6, Rab27A) in GSIS. Activation of these signalling proteins promotes cytoskeletal remodeling, transport and docking of insulin granules on the plasma membrane for exocytotic secretion of insulin. Evidence in rodent and human islets suggests key roles for lipidation (farnesylation and geranylgeranylation) of these G-proteins for their targeting to appropriate cellular compartments for optimal regulation of effectors leading to GSIS...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28871263/the-activity-of-the-neutral-sphingomyelinase-is-important-in-t-cell-recruitment-and-directional-migration
#16
Lena Collenburg, Niklas Beyersdorf, Teresa Wiese, Christoph Arenz, Essa M Saied, Katrin Anne Becker-Flegler, Sibylle Schneider-Schaulies, Elita Avota
Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM) has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28870270/resistance-towards-monensin-is-proposed-to-be-acquired-in-a-toxoplasma-gondii-model-by-reduced-invasion-and-egress-activities-in-addition-to-increased-intracellular-replication
#17
Ahmed Thabet, Johannes Schmidt, Sven Baumann, Walther Honscha, Martin VON Bergen, Arwid Daugschies, Berit Bangoura
Monensin (Mon) is an anticoccidial polyether ionophore widely used to control coccidiosis. The extensive use of polyether ionophores on poultry farms resulted in widespread resistance, but the underlying resistance mechanisms are unknown in detail. For analysing the mode of action by which resistance against polyether ionophores is obtained, we induced in vitro Mon resistance in Toxoplasma gondii-RH strain (MonR-RH) and compared it with the sensitive parental strain (Sen-RH). The proteome assessment of MonR-RH and Sen-RH strains was obtained after isotopic labelling using stable isotope labelling by amino acid in cell culture...
September 5, 2017: Parasitology
https://www.readbyqxmd.com/read/28865032/regulation-of-skeletal-myoblast-differentiation-by-drebrin
#18
Robert S Krauss
Myoblast differentiation is a complex process. As myoblasts differentiate into myofibers, they acquire a cell type-specific transcriptional program, irreversibly exit the cell cycle, and dramatically change their morphology. The morphological changes include cell elongation, alignment, and fusion into syncytial myofibers. Several lines of evidence suggest that these events may be co-regulated. However, the mechanisms that coordinate major alterations in a cell's transcriptome and its shape are not well understood...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28865016/cell-shape-change-by-drebrin
#19
Kensuke Hayashi
Drebrin is localized in actin-rich regions of neuronal and non-neuronal cells. In mature neurons, its localization is strictly restricted to the postsynaptic sites. In order to understand the function of drebrin in cells, many studies have been performed to examine the effect of overexpression or knocking down of drebrin in various cell types, including neurons, myoblasts, kidney cells, and intestinal epithelial cells. In most cases alteration of cell shape and impairment or facilitation of actin-based activities of these cells were observed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28859089/flavin-monooxygenases-regulate-caenorhabditis-elegans-axon-guidance-and-growth-cone-protrusion-with-unc-6-netrin-signaling-and-rac-gtpases
#20
Mahekta R Gujar, Aubrie M Stricker, Erik A Lundquist
The guidance cue UNC-6/Netrin regulates both attractive and repulsive axon guidance. Our previous work showed that in C. elegans, the attractive UNC-6/Netrin receptor UNC-40/DCC stimulates growth cone protrusion, and that the repulsive receptor, an UNC-5:UNC-40 heterodimer, inhibits growth cone protrusion. We have also shown that inhibition of growth cone protrusion downstream of the UNC-5:UNC-40 repulsive receptor involves Rac GTPases, the Rac GTP exchange factor UNC-73/Trio, and the cytoskeletal regulator UNC-33/CRMP, which mediates Semaphorin-induced growth cone collapse in other systems...
August 2017: PLoS Genetics
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