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Gabriela M Soares, Lucas Zangerolamo, Elis G Azevedo, Jose M Costa-Júnior, Everardo M Carneiro, Sara T Saad, Antonio C Boschero, Helena C Barbosa-Sampaio
GTPase activating proteins (GAPs) are ubiquitously expressed, and their role in cellular adhesion and membrane traffic processes have been well described. TBC1D1, which is a Rab-GAP, is necessary for adequate glucose uptake by muscle cells, whereas increased TCGAP, which is a Rho-GAP, decreases GLUT4 translocation, and consequently glucose uptake in adipocytes. Here, we assessed the possible involvement of ARHGAP21, a Rho-GAP protein, in glucose homeostasis. For this purpose, wild type mice and ARHGAP21 transgenic whole-body gene-deficiency mice (heterozygous mice, expressing approximately 50% of ARHGAP21) were fed either chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD)...
March 25, 2018: Journal of Cellular Physiology
Juliana Xavier-Ferrucio, Lauremília Ricon, Karla Vieira, Ana Leda Longhini, Mariana Lazarini, Carolina Louzão Bigarella, Gilberto Franchi, Diane S Krause, Sara T O Saad
Arhgap21 is a member of the Rho GTPase activating protein (RhoGAP) family, which function as negative regulators of Rho GTPases. Arhgap21 has been implicated in adhesion and migration of cancer cells. However, the role of Arhgap21 has never been investigated in hematopoietic cells. Herein, we evaluated functional aspects of hematopoietic stem and progenitor cells (HSPC) using a haploinsufficient (Arhgap21+/- ) mouse. Our results show that Arhgap21+/- mice have an increased frequency of phenotypic HSC, impaired ability to form progenitor colonies in vitro and decreased hematopoietic engraftment in vivo, along with a decrease in LSK cell frequency during serial bone marrow transplantation...
November 23, 2017: Stem Cell Research
Biruhalem Taye, Dawn Yeo, Raphael Tze Chuen Lee, Boon Huan Tan, Richard J Sugrue, Sebastian Maurer-Stroh
Low pathogenic avian influenza (LPAI) viruses are a source of sporadic human infections and could also contribute to future pandemic outbreaks but little is known about inter-species differences in the host responses to these viruses. Here, we studied host gene expression signatures of cell lines from three species (human, chicken, and canine) in response to six different viruses (H1N1/WSN, H5N2/F59, H5N2/F118, H5N2/F189, H5N3 and H9N2). Comprehensive microarray probe set re-annotation and ortholog mapping of the host genes was necessary to allow comparison over extended functionally annotated gene sets and orthologous pathways...
November 1, 2017: International Journal of Molecular Sciences
Yuliya Zilberman, Joshua Abrams, Dorian C Anderson, Jeremy Nance
During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation...
November 6, 2017: Journal of Cell Biology
Kyousuke Kobayashi, Fumiko Suemasa, Hiroshi Sagara, Shinya Nakamura, Yasushi Ino, Kazuyoshi Kobayashi, Hiroaki Hiramatsu, Takeshi Haraguchi, Kazuo Kurokawa, Tomoki Todo, Akihiko Nakano, Hideo Iba
Because several studies have shown that exogenous miR-199a has antiviral effects against various viruses, including herpesviruses, we examined how miR-199a exerts its antiviral effects using epithelial tumour cell lines infected with herpes simplex virus-1 (HSV-1). We found that both miR-199a-5p and -3p impair the secondary envelopment of HSV-1 by suppressing their common target, ARHGAP21, a Golgi-localized GTPase-activating protein for Cdc42. We further found that the trans-cisternae of the Golgi apparatus are a potential membrane compartment for secondary envelopment...
July 27, 2017: Scientific Reports
Arman Javadi, Ravi K Deevi, Emma Evergren, Elodie Blondel-Tepaz, George S Baillie, Mark Gh Scott, Frederick C Campbell
PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signaling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42 -dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here, we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis...
July 27, 2017: ELife
Anna Doraczynska-Kowalik, Kamil H Nelke, Wojciech Pawlak, Maria M Sasiadek, Hanna Gerber
Mandibular prognathism is defined as an abnormal forward projection of the mandible beyond the standard relation to the cranial base and it is usually categorized as both a skeletal Class III pattern and Angle Class III malocclusion. The etiology of mandibular prognathism is still uncertain, with various genetic, epigenetic, and environmental factors possibly involved. However, many reports on its coexistence in both twins and segregation in families suggest the importance of genetic influences. A multifactorial and polygenic background with a threshold for expression or an autosomal dominant mode with incomplete penetrance and variable expressivity are the most probable inheritance patterns...
July 2017: Journal of Craniofacial Surgery
Cole A Weaver, Steven F Miller, Clarissa S G da Fontoura, George L Wehby, Brad A Amendt, Nathan E Holton, Veeratrishul Allareddy, Thomas E Southard, Lina M Moreno Uribe
INTRODUCTION: Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion...
March 2017: American Journal of Orthodontics and Dentofacial Orthopedics
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
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