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https://www.readbyqxmd.com/read/28641386/the-neurosteroid-pregnenolone-reverts-microtubule-derangement-induced-by-the-loss-of-a-functional-cdkl5-iqgap1-complex
#1
Isabella Barbiero, Diana Peroni, Marco Tramarin, Chetan Chandola, Laura Rusconi, Nicoletta Landsberger, Charlotte Kilstrup-Nielsen
CDKL5 is a protein kinase that plays a key role for neuronal functions as testified by the onset of complex neuronal dysfunctions in patients with genetic lesions in CDKL5. Here we identify a novel interactor of CDKL5, IQGAP1, a fundamental regulator of cell migration and polarity. In accordance with a functional role of this interaction, depletion of CDKL5 impairs cell migration and impedes the localization of IQGAP1 at the leading edge. Moreover, we demonstrate that CDKL5 is required for IQGAP1 to form a functional complex with its effectors, Rac1 and the microtubule plus end tracking protein CLIP170...
June 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28639351/titanium-released-from-dental-implant-enhances-pre-osteoblast-adhesion-by-ros-modulating-crucial-intracellular-pathways
#2
M C Rossi, Fjb Bezerra, R A Silva, B P Crulhas, Cjc Fernandes, A S Nascimento, V A Pedrosa, P Padilha, W F Zambuzzi
It is important to understand the cellular and molecular events that occur at the cell-material interface of implants used for bone repair. The mechanisms involved in the initial stages of osteoblast interactions with the surface of the implant material must be decisive for cell fating surrounding them. In order to address this issue, we decided to investigate if conditioned medium for dental implants was able to modulate murine pre-osteoblast metabolism. First, we determined the concentration of titanium (Ti)-containing conditioned medium and found that it was 2-fold increased (p<0...
June 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28638915/-optogenetic-activation-of-dorsal-hippocampal-astrocytic-rac1-blocks-the-learning-of-associative-memory
#3
Xiao-Mu Guo, Zhao-Hui Liao, Ye-Zheng Tao, Fei-Fei Wang, Lan Ma
Rac1 belongs to the family of Rho GTPases, and plays important roles in the brain function. It affects the cell migration and axon guidance via regulating the cytoskeleton and cellular morphology. However, the effect of its dynamic activation in regulating physiological function remains unclear. Recently, a photoactivatable analogue of Rac1 (PA-Rac1) has been developed, allowing the activation of Rac1 by the specific wavelength of light in living cells. Thus, we constructed recombinant adeno-associated virus (AAV) of PA-Rac1 and its light-insensitive mutant PA-Rac1-C450A under the control of the mouse glial fibrillary acidic protein (mGFAP) promoter to manipulate Rac1 activity in astrocytes by optical stimulation...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#4
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28630256/the-small-gtpase-rac1-contributes-to-extinction-of-aversive-memories-of-drug-withdrawal-by-facilitating-gabaa-receptor-endocytosis-in-the-vmpfc
#5
Wei-Sheng Wang, Yun-Yue Ju, Qi-Xin Zhou, Jian-Xin Tang, Meng Li, Lei Zhang, Shuo Kang, Zhong-Guo Chen, Yu-Jun Wang, Hui Ji, Yu-Qiang Ding, Lin Xu, Jing-Gen Liu
Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABAA receptor (GABAAR) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28630074/the-enterohaemorrhagic-escherichia-coli-effector-espw-triggers-actin-remodeling-in-a-rac1-dependent-manner
#6
Pamela Sandu, Valerie F Crepin, Hauke Drechsler, Andrew D McAinsh, Gad Frankel, Cedric N Berger
Enterohaemorrhagic Escherichia coli (EHEC) is a diarrheagenic pathogen that colonizes the gut mucosa and induces attaching-and-effacing lesions. EHEC employs a type III secretion system (T3SS) to translocate 50 effector proteins that hijack and manipulate host cell signalling pathways, which allow bacterial colonization, subversion of immune responses and disease progression. The aim of this study was to characterize the T3SS effector EspW. We found espW in the sequenced O157:H7 and non-O157 EHEC strains as well as in Shigella boydii Furthermore, a truncated version of EspW, containing the first 206 residues is present in EPEC strains belonging to serotype O55:H7...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28627346/-study-on-rac1-mapk-erk-pathway-mediated-mechanism-and-role-in-rats-with-ventilator-induced-lung-injury
#7
Guanghua Tao, Linghui Pan, Ren Jing, Fei Lin, Huijun Dai, Wanyun Ge
OBJECTIVE: To investigate the role of Ras-related C3 botulinum toxin substrate 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (Rac1/MAPK/ERK) signal pathway in rats with ventilator induced lung injury (VILI) and its mechanism. METHODS: Thirty Sprague-Dawley (SD) rats were randomly divided into spontaneous respiration group, normal tidal volume (VT) group and high VT group with 10 rats in each group. The rats in spontaneous respiration group were kept their spontaneous breathing...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28626389/rac1-guides-porf-2-to-wnt-pathway-to-mediate-neural-stem-cell-proliferation
#8
Xi-Tao Yang, Guo-Hui Huang, Hong-Jiang Li, Zhao-Liang Sun, Nan-Jie Xu, Dong-Fu Feng
The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of β-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28624895/semaphorin4d-plexinb1-signaling-attenuates-photoreceptor-outer-segment-phagocytosis-by-reducing-rac1-activity-of-rpe-cells
#9
Ayelen Bulloj, Arvydas Maminishkis, Masayuki Mizui, Silvia C Finnemann
Semaphorins form a family of secreted and membrane-bound molecules that were identified originally as axonal guidance factors during neuronal development. Given their wide distribution in many including mature tissues, semaphorin 4D (sema4D) and its main functional receptor plexin B1 (plxnB1) are expected to fulfill additional functions that remain to be uncovered. A main characteristic of the plexin receptor family is its ability to reorganize the cytoskeleton. PlxnB1 specifically may directly interact with Rho family GTPases to regulate F-actin driven pathways in cells in culture...
June 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28622072/new-model-for-the-interaction-of-iqgap1-with-cdc42-and-rac1
#10
Kazem Nouri, David J Timson, Mohammad R Ahmadian
The specific and rapid formation of protein complexes, involving IQGAP family proteins, is essential for diverse cellular processes, such as adhesion, polarization, and directional migration. Although CDC42 and RAC1, prominent members of the RHO GTPase family, have been implicated in binding to and activating IQGAP1, the exact nature of this protein-protein recognition process has remained obscure. Here, we propose a mechanistic framework model that is based on a multiple-step binding process, which is a prerequisite for the dynamic functions of IQGAP1 as a scaffolding protein and a critical mechanism in temporal regulation and integration of cellular pathways...
June 16, 2017: Small GTPases
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#11
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620941/endothelial-mechanotransduction-proteins-and-vascular-function-are-altered-by-dietary-sucrose-supplementation-in-healthy-young-male-subjects
#12
Lasse Gliemann, Nicolai Rytter, Mads Lindskrog, Martina H Lundberg Slingsby, Thorbjörn Åkerström, Lykke Sylow, Erik A Richter, Ylva Hellsten
Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, twelve young healthy male subjects supplemented their diet with 3 × 75 g sucrose day(-1) for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler...
June 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28614361/molecular-cloning-characterization-and-expression-analysis-of-frizzled-6-in-the-small-intestine-of-pigs-sus-scrofa
#13
Lijun Zou, Xiaocheng Wang, Liping Jiang, Shengping Wang, Xia Xiong, Huansheng Yang, Wei Gao, Min Gong, Chien-An A Hu, Yulong Yin
Frizzled 6 (FZD6) encodes an integral membrane protein that functions in multiple signal transduction pathways, for example, as a receptor in Wnt/planar cell polarity (PCP) signaling pathway for polarized cell migration and organ morphogenesis. Mutations in FZD6 have been identified in a variety of tumors. In this study, the full-length cDNA of Sus scrofa FZD6 (Sfz6) was cloned and characterized. Nucleotide sequence analysis demonstrates that the Sfz6 gene encodes the 712 amino-acid (aa) protein with seven transmembrane domain...
2017: PloS One
https://www.readbyqxmd.com/read/28609201/opposite-functions-of-stat3-and-smad3-in-regulating-tiam1-expression-in-th17-cells
#14
Thomas Buttrick, Samia J Khoury, Wassim Elyaman
We recently showed that Tiam1 expression is induced in pro-inflammatory T helper 17 (Th17) cells differentiated with interleukin (IL)-6 and TGF-β1, and together with Rac1 promote Th17 cell development and autoimmunity in a mouse model of multiple sclerosis. Here we found that STAT3 and Smad3, downstream transcription factors of IL-6 and TGF-β1, respectively, play opposing roles in regulating Tiam1 transcription in CD4(+) T-cells. While IL-6-STAT3 signaling promotes Tiam1 expression, TGF-β1-Smad3 induces the opposite outcome...
June 13, 2017: Small GTPases
https://www.readbyqxmd.com/read/28608476/pro-migratory-and-tgf-%C3%AE-activating-functions-of-%C3%AE-v%C3%AE-6-integrin-in-pancreatic-cancer-are-differentially-regulated-via-an-eps8-dependent-gtpase-switch
#15
Jo Tod, Christopher J Hanley, Mark R Morgan, Marta Rucka, Toby Mellows, Maria-Antoinette Lopez, Philip Kiely, Karwan A Moutasim, Steven J Frampton, Durgagauri Sabnis, David R Fine, Colin Johnson, John F Marshall, Giorgio Scita, Veronika Jenei, Gareth J Thomas
The integrin αvβ6 is upregulated in numerous carcinomas, where expression commonly correlates with poor prognosis. αvβ6 promotes tumour invasion, partly through regulation of proteases and cell migration, and is also the principal mechanism by which epithelial cells activate TGF-β1; this latter function complicates therapeutic targeting of αvβ6, since TGF-β1 has both tumour-promoting and -suppressive effects. It is unclear how these different αvβ6 functions are linked; both require actin cytoskeletal reorganisation, and it is suggested that tractive forces generated during cell migration activate TGF-β1 by exerting mechanical tension on the ECM-bound latent complex...
June 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28602951/ced-10-wasp-arp2-3-signaling-axis-regulates-apoptotic-cell-corpse-engulfment-in-c-elegans
#16
Dou Wu, Yongping Chai, Zhiwen Zhu, Wenjing Li, Guangshuo Ou, Wei Li
Efficient clearance of apoptotic cells is essential for tissue homeostasis in metazoans. Genetic studies in Caenorhabditis elegans have identified signaling cascades that activate CED-10/Rac1 GTPase and promote actin cytoskeletal rearrangement during apoptotic cell engulfment. However, the molecular connection between CED-10 activation and actin reorganization remains elusive. Here, we provide evidence that CED-10 binds to the Arp2/3 nucleation promoting factor WASP; CED-10 recruits WASP and Arp2/3 to apoptotic cell corpses in the phagocytes...
June 9, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28602209/update-on-glut4-vesicle-traffic-a-cornerstone-of-insulin-action
#17
REVIEW
Javier R Jaldin-Fincati, Martin Pavarotti, Scott Frendo-Cumbo, Philip J Bilan, Amira Klip
Glucose transport is rate limiting for dietary glucose utilization by muscle and fat. The glucose transporter GLUT4 is dynamically sorted and retained intracellularly and redistributes to the plasma membrane (PM) by insulin-regulated vesicular traffic, or 'GLUT4 translocation'. Here we emphasize recent findings in GLUT4 translocation research. The application of total internal reflection fluorescence microscopy (TIRFM) has increased our understanding of insulin-regulated events beneath the PM, such as vesicle tethering and membrane fusion...
June 8, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28601637/necl-4-enhances-the-plc%C3%AE-c-raf-mek-erk-pathway-without-affecting-internalization-of-vegfr2
#18
Shota Yamana, Amina Tokiyama, Hidenobu Fujita, Yuya Terao, Sayo Horibe, Naoto Sasaki, Seimi Satomi-Kobayashi, Ken-Ichi Hirata, Yoshiyuki Rikitake
We have reported that knockdown of Necl-4 decreases vascular endothelial growth factor (VEGF)-induced phosphorylation of extracellular signal-regulated kinase (ERK) without affecting phosphorylation of VEGF receptor 2 (VEGFR2) in sparsely cultured human umbilical vein endothelial cells (HUVECs). However, the underlying molecular mechanism is unknown. Compared with control HUVECs, VEGF-induced phosphorylation of phospholipase Cγ (PLCγ), c-Raf, mitogen-activated protein kinase/ERK kinase (MEK) and ERK were all inhibited in Necl-4-knockdown HUVECs...
June 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28601080/microrna-630-suppresses-epithelial-to-mesenchymal-transition-by-regulating-foxm1-in-gastric-cancer-cells
#19
Jing Feng, Xiaojuan Wang, Weihua Zhu, Si Chen, Changwei Feng
In the present study, we investigated the functional role of microRNA (miR)-630 in epithelial-to-mesenchymal transition (EMT) of gastric cancer (GC) cells, as well as the regulatory mechanism. Cells of human GC cell line SGC 7901 were transfected with miR-630 mimic or miR-630 inhibitor. The transfection efficiency was confirmed by qRT-PCR. Cell migration and invasion were determined by Transwell assay. Protein expression of E-cadherin, vimentin, and Forkhead box protein M1 (FoxM1) was tested by Western blot...
June 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28600322/rac1-switching-at-the-right-time-and-location-is-essential-for-fc%C3%AE-receptor-mediated-phagosome-formation
#20
Yuka Ikeda, Katsuhisa Kawai, Akira Ikawa, Kyoko Kawamoto, Youhei Egami, Nobukazu Araki
Lamellipodia are sheet-like cell protrusions driven by actin polymerization mainly through Rac1, a GTPase molecular switch. In Fcγ receptor-mediated phagocytosis of IgG-opsonized erythrocytes (IgG-Es), Rac1 activation is required for lamellipodial extension along the surface of IgG-Es. However, the significance of Rac1 deactivation in phagosome formation is poorly understood. Our live-cell imaging and electron microscopy revealed that RAW264 macrophages expressing a constitutively active Rac1 mutant showed defects in phagocytic cup formation, while lamellipodia were formed around IgG-Es...
June 9, 2017: Journal of Cell Science
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