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Liang Zhang, Valbona Luga, Sarah K Armitage, Martin Musiol, Amy Won, Christopher M Yip, Sergey V Plotnikov, Jeffrey L Wrana
Cell migration is fundamental for both physiological and pathological processes. Migrating cells usually display high dynamics in morphology, which is orchestrated by an integrative array of signalling pathways. Here we identify a novel pathway, we term lateral signalling, comprised of the planar cell polarity (PCP) protein Pk1 and the RhoGAPs, Arhgap21/23. We show that the Pk1-Arhgap21/23 complex inhibits RhoA, is localized on the non-protrusive lateral membrane cortex and its disruption leads to the disorganization of the actomyosin network and altered focal adhesion dynamics...
2016: Nature Communications
ShiGang Yu, WeiWei Chu, LiFan Zhang, HouMing Han, RongXue Zhao, Wei Wu, JiangNing Zhu, Michael V Dodson, Wei Wei, HongLin Liu, Jie Chen
Laying performance is an important economical trait of goose production. As laying performance is of low heritability, it is of significance to develop a marker-assisted selection (MAS) strategy for this trait. Definition of sequence variation related to the target trait is a prerequisite of quantitating MAS, but little is presently known about the goose genome, which greatly hinders the identification of genetic markers for the laying traits of geese. Recently developed restriction site-associated DNA (RAD) sequencing is a possible approach for discerning large-scale single nucleotide polymorphism (SNP) and reducing the complexity of a genome without having reference genomic information available...
2015: PloS One
Sandra Mara Ferreira, Gustavo Jorge Santos, Luiz F Rezende, Luciana Mateus Gonçalves, Junia Carolina Santos-Silva, Carolina Louzão Bigarella, Everardo Magalhães Carneiro, Sara Teresinha Ollala Saad, Antonio Carlos Boschero, Helena Cristina Barbosa-Sampaio
AIMS: ARHGAP21 is a Rho GTPase-activating protein (RhoGAP) that associates with many proteins and modulates several cellular functions, including actin cytoskeleton rearrangement in different tissues. However, it is unknown whether ARHGAP21 is expressed in pancreatic beta cells and its function in these cells. Herein, we assess the participation of ARHGAP21 in insulin secretion. MAIN METHODS: Neonatal mice were treated with anti-sense oligonucleotide against ARHG AP21 (AS) for 2 days, resulting in a reduction of the protein's expression of about 60% in the islets...
April 15, 2015: Life Sciences
L Perillo, A Monsurrò, E Bonci, A Torella, M Mutarelli, V Nigro
Mandibular prognathism (MP) is a recognizable phenotype associated with dentoskeletal class III malocclusion. MP is a complex genetic trait, although familial recurrence also suggests the contribution of single inherited variations. To date, the genetic causes of MP have been investigated using linkage analysis or association studies in pooled families. Here for the first time, next-generation sequencing was used to study a single family with a large number of MP-affected members and to identify MP-related candidate genes...
April 2015: Journal of Dental Research
Nicholas C Wong, Vivek A Bhadri, Jovana Maksimovic, Mandy Parkinson-Bates, Jane Ng, Jeff M Craig, Richard Saffery, Richard B Lock
BACKGROUND: Patient-derived tumour xenografts are an attractive model for preclinical testing of anti-cancer drugs. Insights into tumour biology and biomarkers predictive of responses to chemotherapeutic drugs can also be gained from investigating xenograft models. As a first step towards examining the equivalence of epigenetic profiles between xenografts and primary tumours in paediatric leukaemia, we performed genome-scale DNA methylation and gene expression profiling on a panel of 10 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) tumours that were stratified by prednisolone response...
2014: BMC Genomics
Mark L Schultz, Luis Tecedor, Colleen S Stein, Mark A Stamnes, Beverly L Davidson
Juvenile Batten disease (juvenile neuronal ceroid lipofuscinosis, JNCL) is a devastating neurodegenerative disease caused by mutations in CLN3, a protein of undefined function. Cell lines derived from patients or mice with CLN3 deficiency have impairments in actin-regulated processes such as endocytosis, autophagy, vesicular trafficking, and cell migration. Here we demonstrate the small GTPase Cdc42 is misregulated in the absence of CLN3, and thus may be a common link to multiple cellular defects. We discover that active Cdc42 (Cdc42-GTP) is elevated in endothelial cells from CLN3 deficient mouse brain, and correlates with enhanced PAK-1 phosphorylation, LIMK membrane recruitment, and altered actin-driven events...
2014: PloS One
Nelly Pirot, Hélène Delpech, Virginie Deleuze, Christiane Dohet, Monique Courtade-Saïdi, Céline Basset-Léobon, Elias Chalhoub, Danièle Mathieu, Valérie Pinet
Maturation of newly formed vessels is a multistep phenomenon during which functional endothelial barriers are established. Disruption of vessel integrity is an important feature in many physiological and pathological processes. We previously reported that lymphoblastic leukemia-derived sequence 1 (LYL1) is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. In this study, we show that LYL1 is also required during the formation of the mature endothelial barrier in the lungs of adult mice...
April 15, 2014: American Journal of Physiology. Lung Cellular and Molecular Physiology
Xiaojuan Chi, Song Wang, Yifan Huang, Jilong Chen
Influenza virus assembly requires the completion of viral protein and vRNP transport to the assembly site at the plasma membrane. Therefore, efficient regulation of intracellular transport of the viral proteins and vRNPs to the surface of the host cell is especially important for virus morphogenesis. Influenza A virus uses the machineries of host cells to transport its own components including ribonucleoproteins (vRNPs) and three transmembrane proteins hemagglutinin (HA), neuraminidase (NA) and matrix 2 protein (M2)...
September 2012: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Karin S A Barcellos, Carolina L Bigarella, Mark V Wagner, Karla P Vieira, Mariana Lazarini, Peter R Langford, João A Machado-Neto, Steven G Call, Davis M Staley, Jarom Y Chung, Marc D Hansen, Sara T O Saad
Cell-cell adhesions and the cytoskeletons play important and coordinated roles in cell biology, including cell differentiation, development, and migration. Adhesion and cytoskeletal dynamics are regulated by Rho-GTPases. ARHGAP21 is a negative regulator of Rho-GTPases, particularly Cdc42. Here we assess the function of ARHGAP21 in cell-cell adhesion, cell migration, and scattering. We find that ARHGAP21 is localized in the nucleus, cytoplasm, or perinuclear region but is transiently redistributed to cell-cell junctions 4 h after initiation of cell-cell adhesion...
January 25, 2013: Journal of Biological Chemistry
Mariana Lazarini, Fabiola Traina, João A Machado-Neto, Karin S A Barcellos, Yuri B Moreira, Marcelo M Brandão, Sergio Verjovski-Almeida, Anne J Ridley, Sara T Olalla Saad
BACKGROUND: Several Rho GTPase-activating proteins (RhoGAPs) are implicated in tumor progression through their effects on Rho GTPase activity. ARHGAP21 is a RhoGAP with increased expression in head and neck squamous cell carcinoma and with a possible role in glioblastoma tumor progression, yet little is known about the function of ARHGAP21 in cancer cells. Here we studied the role of ARHGAP21 in two prostate adenocarcinoma cell lines, LNCaP and PC3, which respectively represent initial and advanced stages of prostate carcinogenesis...
February 2013: Biochimica et Biophysica Acta
Carolina L Bigarella, Karla P Vieira Ferro, Karin S A Barcellos, Daniel Martins-de-Souza, Fabiola Traina, José C Novello, Sara T Olalla Saad, Leticia Fröhlich Archangelo
ARHGAP21 is a 217 kDa RhoGAP protein shown to modulate cell migration through the control of Cdc42 and FAK activities. In the present work a 250 kDa-ARHGAP21 was identified by mass spectrometry. This modified form is differentially expressed among cell lines and human primary cells. Co-immunoprecipitations and in vitro SUMOylation confirmed ARHGAP21 specific modification by SUMO2/3 and mapped the SUMOylation site to ARHGAP21 lysine K1443. Immunofluorescence staining revealed that ARHGAP21 co-localizes with SUMO2/3 in the cytoplasm and membrane compartments...
September 21, 2012: FEBS Letters
Song Wang, Hua Li, Yuhai Chen, Haitao Wei, George F Gao, Hongqiang Liu, Shile Huang, Ji-Long Chen
Influenza virus neuraminidase (NA) is transported to the virus assembly site at the plasma membrane and is a major viral envelope component that plays a critical role in the release of progeny virions and in determination of host range restriction. However, little is known about the host factors that are involved in regulating the intracellular and cell surface transport of NA. Here we identified the Cdc42-specific GAP, ARHGAP21 differentially expressed in host cells infected with influenza A virus using cDNA microarray analysis...
March 23, 2012: Journal of Biological Chemistry
D F Anthony, Y Y Sin, S Vadrevu, N Advant, J P Day, A M Byrne, M J Lynch, G Milligan, M D Houslay, G S Baillie
Activation of the small GTPase RhoA following angiotensin II stimulation is known to result in actin reorganization and stress fiber formation. Full activation of RhoA, by angiotensin II, depends on the scaffolding protein β-arrestin 1, although the mechanism behind its involvement remains elusive. Here we uncover a novel partner and function for β-arrestin 1, namely, in binding to ARHGAP21 (also known as ARHGAP10), a known effector of RhoA activity, whose GTPase-activating protein (GAP) function it inhibits...
March 2011: Molecular and Cellular Biology
Heidi Hehnly, Weidong Xu, Ji-Long Chen, Mark Stamnes
The molecular mechanisms underlying cytoskeleton-dependent Golgi positioning are poorly understood. In mammalian cells, the Golgi apparatus is localized near the juxtanuclear centrosome via dynein-mediated motility along microtubules. Previous studies implicate Cdc42 in regulating dynein-dependent motility. Here we show that reduced expression of the Cdc42-specific GTPase-activating protein, ARHGAP21, inhibits the ability of dispersed Golgi membranes to reposition at the centrosome following nocodazole treatment and washout...
August 2010: Traffic
Heidi Hehnly, Katrina Marie Longhini, Ji-Long Chen, Mark Stamnes
Shiga-toxin-producing Escherichia coli remain a food-borne health threat. Shiga toxin is endocytosed by intestinal epithelial cells and transported retrogradely through the secretory pathway. It is ultimately translocated to the cytosol where it inhibits protein translation. We found that Shiga toxin transport through the secretory pathway was dependent on the cytoskeleton. Recent studies reveal that Shiga toxin activates signaling pathways that affect microtubule reassembly and dynein-dependent motility. We propose that Shiga toxin alters cytoskeletal dynamics in a way that facilitates its transport through the secretory pathway...
October 2009: Molecular Biology of the Cell
Carolina Louzão Bigarella, Luciene Borges, Fernando Ferreira Costa, Sara Terezinha Olalla Saad
Glioblastoma multiforme is highly aggressive and is the most common glial tumor type. Although there have been advances in treatment, the average survival expectancy is 12-15 months. Several genes have been shown to influence glioblastoma progression. In the present work, we demonstrate that the RhoGTPase Activating Protein 21 (ARHGAP21) is expressed in the nuclear and perinuclear regions of several cell lines. In T98G and U138MG, glioblastoma derived cell lines, ARHGAP21 interacts with the C-terminal region of Focal Adhesion Kinase (FAK)...
May 2009: Biochimica et Biophysica Acta
Luciene Borges, Carolina Louzão Bigarella, Mariana Ozello Baratti, Daniella P Crosara-Alberto, Paulo P Joazeiro, Kleber G Franchini, Fernando F Costa, Sara Teresinha Olalla Saad
ARHGAP21 is highly expressed in the heart, which demonstrates activity over Cdc42 and interacts with proteins of the cytoskeleton and adherent junctions. The main cause of cardiac hypertrophy is mechanical stimulus; therefore we analyzed ARHGAP21 expression after acute mechanical stress in the myocardium and its association with FAK and PKCzeta. We demonstrated that ARHGAP21 is relocated to Z-lines and costameres after pressure overload, and interacts with PKCzeta and FAK in control rats (sham), rats submitted to aortic clamping and spontaneously hypertensive rats (SHR)...
October 3, 2008: Biochemical and Biophysical Research Communications
Julie Ménétrey, Mylène Perderiset, Jérome Cicolari, Thierry Dubois, Nadia Elkhatib, Fatima El Khadali, Michel Franco, Philippe Chavrier, Anne Houdusse
ARHGAP21 is a Rho family GTPase-activating protein (RhoGAP) that controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. ARHGAP21 is recruited to the Golgi by binding to another small GTPase, ARF1. Here, we present the crystal structure of the activated GTP-bound form of ARF1 in a complex with the Arf-binding domain (ArfBD) of ARHGAP21 at 2.1 A resolution. We show that ArfBD comprises a PH domain adjoining a C-terminal alpha helix, and that ARF1 interacts with both of these structural motifs through its switch regions and triggers structural rearrangement of the PH domain...
April 4, 2007: EMBO Journal
A Carles, R Millon, A Cromer, G Ganguli, F Lemaire, J Young, C Wasylyk, D Muller, I Schultz, Y Rabouel, D Dembélé, C Zhao, P Marchal, C Ducray, L Bracco, J Abecassis, O Poch, B Wasylyk
Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples...
March 16, 2006: Oncogene
Yuriko Katoh, Masaru Katoh
ARHGAP1, ARHGAP2, ARHGAP3, ARHGAP4, ARHGAP5, ARHGAP6, ARHGAP7 (DLC1), ARHGAP8, ARHGAP9, ARHGAP10, ARHGAP12, ARHGAP13 (SRGAP1), ARHGAP14 (SRGAP2), ARHGAP15, ARHGAP17 (RICH1), ARHGAP18, ARHGAP19, ARHGAP20, ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP26, STARD13 (DLC2), HA-1, GMIP, PARG1, RACGAP1, PIK3R1, PIK3R2, and FNBP2 genes encode Rho/Rac/Cdc42-like GTPase activating (RhoGAP) proteins. Here, we characterized human ARHGAP27 gene by using bioinformatics. Complete coding sequence of ARHGAP27 isoform 1, encoding a full-length 889-aa protein, was determined by assembling exon 1 (nucleotide position 143440-144096 of AC091132...
November 2004: International Journal of Molecular Medicine
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