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Cdc42

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https://www.readbyqxmd.com/read/28643773/a-cdc42-rhoa-regulatory-circuit-downstream-of-glycoprotein-ib-guides-transendothelial-platelet-biogenesis
#1
Sebastian Dütting, Frederique Gaits-Iacovoni, David Stegner, Michael Popp, Adrien Antkowiak, Judith M M van Eeuwijk, Paquita Nurden, Simon Stritt, Tobias Heib, Katja Aurbach, Oguzhan Angay, Deya Cherpokova, Niels Heinz, Ayesha A Baig, Maximilian G Gorelashvili, Frank Gerner, Katrin G Heinze, Jerry Ware, Georg Krohne, Zaverio M Ruggeri, Alan T Nurden, Harald Schulze, Ute Modlich, Irina Pleines, Cord Brakebusch, Bernhard Nieswandt
Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28642137/overexpression-cdc42-attenuates-isoflurane-induced-neurotoxicity-in-developmental-brain-of-rats
#2
Xi Fang, Shiyong Li, Qiang Han, Yilin Zhao, Jie Gao, Jing Yan, Ailin Luo
Nowadays many children receive operations with general anesthesia. Isoflurane is a commonly-used general anesthetic. Numbers of studies demonstrated that isoflurane induced neurotoxicity and neurobehavioral deficiency in young rats, however, the underlying mechanism remained unknown. Cell division cycle 42 (cdc42) played an important role in regulating synaptic vesicle trafficking and actin dynamics in neuron, which closely linked to synaptic plasticity and dendritic spine formation. Meanwhile, cdc42 also involved in many neurodegenerative diseases...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28636748/e-cadherin-mediates-uvr-and-calcium-induced-melanin-transfer-in-human-skin-cells
#3
Suman K Singh, Richard Baker, Stephen K Sikkink, Carine Nizard, Sylvianne Schnebert, Robin Kurfurst, Desmond J Tobin
Skin pigmentation is directed by epidermal-melanin units, characterized by long-lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously we reported that MC:KC contact is required for melanosome transfer, that this can be enhanced by filopodial and by UVR/UVA irradiation, which can up-regulate melanosome transfer via Myosin X-mediated control of MC filopodia. Both MC and KC express Ca(2+) -dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca(2+) , while ultraviolet radiation (UVR) raises intra-MC Ca(2+) via calcium selective ORAI1 ion channels; both are associated with regulating melanogenesis...
June 21, 2017: Experimental Dermatology
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/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#5
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28633952/chronic-methylphenidate-regulates-genes-and-proteins-mediating-neuroplasticity-in-the-juvenile-rat-brain
#6
Emmanuel Quansah, Tiziana Sgamma, Estabraq Jaddoa, Tyra S C Zetterström
Methylphenidate (MPH) is the front-line psychostimulant medication prescribed for alleviating the symptoms associated with attention deficit hyperactivity disorder (ADHD) in children. Here, we investigated the effects of chronic MPH (2.0mg/kg, twice daily for 15 days) exposure to young rats (20-25days old at start of treatment) on the expression of genes and proteins associated with neuroplasticity, such as activity regulated cytoskeleton-associated protein (Arc), insulin receptor substrate protein 53 (IRSp53), cell division control protein 42 (Cdc42), and actin-related protein 2 (Arp2)...
June 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28626024/intersectin-2-controls-actin-cap-formation-and-meiotic-division-in-mouse-oocytes-through-the-cdc42-pathway
#7
Jiaqi Zhang, Rujun Ma, Ling Li, Lina Wang, Xiaojing Hou, Longsen Han, Juan Ge, Mo Li, Qiang Wang
Intersectins (ITSNs), an evolutionarily conserved adaptor protein family, have been implicated in multiple biologic processes; however, their functions in mammalian oocytes have not been addressed. Here, we report delayed meiotic resumption and defective cytokinesis upon specific depletion of ITSN2 in mouse oocytes. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are readily observed in ITSN2-depleted oocytes. Similarly, a small molecule that targets the Cdc42-ITSN interaction also disrupts oocyte maturation and actin polymerization...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28622072/new-model-for-the-interaction-of-iqgap1-with-cdc42-and-rac1
#8
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/28620131/exosomes-containing-differential-expression-of-microrna-and-mrna-in-osteosarcoma-that-can-predict-response-to-chemotherapy
#9
Ji-Feng Xu, Ya-Ping Wang, Shui-Jun Zhang, Yu Chen, Hai-Feng Gu, Xiao-Fan Dou, Bing Xia, Qing Bi, Shun-Wu Fan
A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611940/involvement-of-chromatin-remodeling-genes-and-the-rho-gtpases-rhob-and-cdc42-in-ovarian-clear-cell-carcinoma
#10
Nicolai Skovbjerg Arildsen, Jenny-Maria Jönsson, Katarina Bartuma, Anna Ebbesson, Sofia Westbom-Fremer, Anna Måsbäck, Susanne Malander, Mef Nilbert, Ingrid A Hedenfalk
OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28607034/tctex-1-controls-ciliary-resorption-by-regulating-branched-actin-polymerization-and-endocytosis
#11
Masaki Saito, Wataru Otsu, Kuo-Shun Hsu, Jen-Zen Chuang, Teruyuki Yanagisawa, Vincent Shieh, Taku Kaitsuka, Fan-Yan Wei, Kazuhito Tomizawa, Ching-Hwa Sung
The primary cilium is a plasma membrane-protruding sensory organelle that undergoes regulated assembly and resorption. While the assembly process has been studied extensively, the cellular machinery that governs ciliary resorption is less well understood. Previous studies showed that the ciliary pocket membrane is an actin-rich, endocytosis-active periciliary subdomain. Furthermore, Tctex-1, originally identified as a cytoplasmic dynein light chain, has a dynein-independent role in ciliary resorption upon phosphorylation at Thr94...
June 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28600358/cell-adhesion-controlled-by-adhesion-g-protein-coupled-receptor-gpr124-adgra2-is-mediated-by-a-protein-complex-comprising-intersectins-and-elmo-dock
#12
Magda Nohemí Hernández-Vásquez, Sendi Rafael Adame-García, Noumeira Hamoud, Rony Chidiac, Guadalupe Reyes-Cruz, Jean Philippe Gratton, Jean-François Côté, José Vázquez-Prado
Developmental angiogenesis and the maintenance of blood brain barrier involve endothelial cell adhesion, which are linked to cytoskeletal dynamics. GPR124 (also known as TEM5/ADGRA2) is an Adhesion GPCR-family member that plays a pivotal role in brain angiogenesis and in ensuring a tight blood-brain barrier. However, the signaling properties of GPR124 remain poorly defined. Here, we show that ectopic expression of GPR124 promotes cell adhesion, additive to extracellular matrix-dependent effect, coupled with filopodia and lamellipodia formation and an enrichment of a pool of the GPCR at actin-rich cellular protrusions containing VASP, a filopodial marker...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28600193/functional-and-molecular-responses-of-the-blue-mussel-mytilus-edulis-hemocytes-exposed-to-cadmium-an-in%C3%A2-vitro-model-and-transcriptomic-approach
#13
Philippine Granger Joly de Boissel, Michel Fournier, Juan Carlos Rodriguez-Lecompte, Patty McKenna, Frederick Kibenge, Ahmed Siah
The bivalve mollusk, Mytilus edulis, is used as a sentinel species in several monitoring programs due to its ability to bio-accumulate contaminants. Its immune system consists of hemocytes and humoral components, which constitute the main part of the hemolymph. The present study is aimed at understanding the effects of Cd on the differentially expressed genes involved in the phagocytosis of M. edulis' hemocytes. Our approach focuses on an in vitro model by exposing hemocytes to different concentrations of Cd ranging from 10(-9) M to 10(-3) M...
June 6, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28596235/epidermal-growth-factor-induced-pyruvate-dehydrogenase-kinase-1-expression-enhances-head-and-neck-squamous-cell-carcinoma-metastasis-via-up-regulation-of-fibronectin
#14
Jinn-Yuan Hsu, Jang-Yang Chang, Kwang-Yu Chang, Wen-Chang Chang, Ben-Kuen Chen
Epidermal growth factor receptor (EGFR) activation is a major cause of metastasis in such cancers as head and neck squamous cell carcinoma (HNSCC); however, whether the metabolic enzyme, pyruvate dehydrogenase kinase 1 (PDK1), mediates EGF-enhanced HNSCC metastasis remains unclear. Of interest, we found that EGF induced PDK1 expression in HNSCC. Tumor cell transformation induced by EGF was repressed by PDK1 knockdown, and the down-regulation of PDK1 expression or inhibition of its activity significantly blocked EGF-enhanced cell migration and invasion...
June 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28574147/the-pak1-signalling-pathway-in-cardiac-disease-from-mechanistic-study-to-therapeutic-exploration
#15
REVIEW
Yanwen Wang, Shunyao Wang, Ming Lei, Mark Boyett, Hoyee Tsui, Wei Liu, Xin Wang
p21-activated kinase 1 (Pak1) is a member of the highly conserved family of serine/threonine protein kinases regulated by Ras-related small G-proteins, Cdc42/Rac1. It has been previously demonstrated to be involved in cardiac protection. Based on recent studies, this review assembles an overview of the role of Pak1 in cardiac diseases including disrupted Ca(2+) homoeostasis related cardiac arrhythmias, β-adrenergic stress and pressure overload-induced hypertrophy, and ischemia/reperfusion injury. These findings demonstrate the importance of Pak1 regulation through phosphorylation and transcriptional modification of hypertrophy and/or arrhythmia-related genes...
June 2, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28571533/cdc42-signaling-pathway-inhibition-as-a-therapeutic-target-in-ras-related-cancers
#16
Byron J Aguilar, Huchen Zhou, Qun Lu
The frequency of pro-oncogenic mutations and development of drug resistance are major challenges for successful Ras-related cancer treatment. Therefore, there is an urgent need to identify novel targets in the Ras-signaling pathway to address these challenges. Cell division cycle protein 42 (Cdc42) is a classical member of the Rho family of small GTPases in the Ras oncogene superfamily. Enhanced Cdc42-signaling facilitates Ras-mediated cellular transformation, tumorigenesis, and metastasis. Cdc42, Ras, and EGFR are involved in an activation loop that prolongs their signaling...
June 1, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28565754/identification-of-potential-biomarkers-of-sepsis-using-bioinformatics-analysis
#17
Yu-Xia Yang, Li Li
Sepsis is defined as the systemic inflammatory response to infection and is one of the leading causes of mortality in critically ill patients. The goal of the present study is to elucidate the molecular mechanism of sepsis. Transcription profile data (GSE12624) were downloaded that had a total of 70 samples (36 sepsis samples and 34 non-sepsis samples) from the Gene Expression Omnibus database. Protein-protein interaction network analysis was conducted in order to comprehensively understand the interactions of genes in all samples...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28564597/synaptic-remodeling-depends-on-signaling-between-serotonin-receptors-and-the-extracellular-matrix
#18
Monika Bijata, Josephine Labus, Daria Guseva, Michał Stawarski, Malte Butzlaff, Joanna Dzwonek, Jenny Schneeberg, Katrin Böhm, Piotr Michaluk, Dmitri A Rusakov, Alexander Dityatev, Grzegorz Wilczyński, Jakub Wlodarczyk, Evgeni Ponimaskin
Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), matrix metalloproteinase 9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5-HT7R and CD44 (identified as an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine remodeling, synaptic pruning, and impairment of long-term potentiation (LTP)...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28562340/cell-type-dependent-hif1-%C3%AE-mediated-effects-of-hypoxia-on-proliferation-migration-and-metastatic-potential-of-human-tumor-cells
#19
Enikő Tátrai, Alexandra Bartal, Alexandra Gacs, Sándor Paku, István Kenessey, Tamás Garay, Balázs Hegedűs, Eszter Molnár, Mihály T Cserepes, Zita Hegedűs, Nóra Kucsma, Gergely Szakács, József Tóvári
Tumor hypoxia promotes neoangiogenesis and contributes to the radio- and chemotherapy resistant and aggressive phenotype of cancer cells. However, the migratory response of tumor cells and the role of small GTPases regulating the organization of cytoskeleton under hypoxic conditions have yet to be established. Accordingly, we measured the proliferation, migration, RhoA activation, the mRNA and protein levels of hypoxia inducible factor-1alpha (HIF-1α) and three small G-proteins, Rac1, cdc42 and RhoA in a panel of five human tumor cell lines under normoxic and hypoxic conditions...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28554775/zonula-occludens-2-regulates-rho-proteins-activity-and-the-development-of-epithelial-cytoarchitecture-and-barrier-function
#20
Arturo Raya-Sandino, Alejandro Castillo-Kauil, Alaide Domínguez-Calderón, Lourdes Alarcón, David Flores-Benitez, Francisco Cuellar-Perez, Bruno López-Bayghen, Bibiana Chávez-Munguía, José Vázquez-Prado, Lorenza González-Mariscal
Silencing Zonula occludens 2 (ZO-2), a tight junctions (TJ) scaffold protein, in epithelial cells (MDCK ZO-2 KD) triggers: 1) Decreased cell to substratum attachment, accompanied by reduced expression of claudin-7 and integrin β1, and increased vinculin recruitment to focal adhesions and stress fibers formation; 2) Lowered cell-cell aggregation and appearance of wider intercellular spaces; 3) Increased RhoA/ROCK activity, mediated by GEF-HI recruitment to cell borders by cingulin; 4) Increased Cdc42 activity, mitotic spindle disorientation and the appearance of cysts with multiple lumens; 5) Increased Rac and cofilin activity, multiple lamellipodia formation and random cell migration but increased wound closure; 6) Diminished cingulin phosphorylation and disappearance of planar network of microtubules at the TJ region; and 7) Increased transepithelial electrical resistance at steady state, coupled to an increased expression of ZO-1 and claudin-4 and a decreased expression of claudin-2 and paracingulin...
May 26, 2017: Biochimica et Biophysica Acta
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