688 results match your criteria guanosine triphosphatases

Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex.

Sci Adv 2021 Jul 21;7(30). Epub 2021 Jul 21.

RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

The dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) promotes cell motility, phagocytosis, and cancer metastasis through activation of Rho guanosine triphosphatases. Engulfment and cell motility (ELMO) proteins are binding partners of DOCK and regulate Rac activation. Here, we report the cryo-electron microscopy structure of the active ELMO1-DOCK5 complex bound to Rac1 at 3. Read More

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An variant links aberrant Rac1 function to early-onset skeletal fragility.

JBMR Plus 2021 Jul 7;5(7):e10509. Epub 2021 Jun 7.

Folkhälsan Institute of Genetics Helsinki Finland.

Ras homologous guanosine triphosphatases (RhoGTPases) control several cellular functions, including cytoskeletal actin remodeling and cell migration. Their activities are downregulated by GTPase-activating proteins (GAPs). Although RhoGTPases are implicated in bone remodeling and osteoclast and osteoblast function, their significance in human bone health and disease remains elusive. Read More

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The RAS GTPase RIT1 compromises mitotic fidelity through spindle assembly checkpoint suppression.

Curr Biol 2021 Jun 30. Epub 2021 Jun 30.

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 3(rd) Street, San Francisco, CA 94158, USA. Electronic address:

The spindle assembly checkpoint (SAC) functions as a sensor of unattached kinetochores that delays mitotic progression into anaphase until proper chromosome segregation is guaranteed. Disruptions to this safety mechanism lead to genomic instability and aneuploidy, which serve as the genetic cause of embryonic demise, congenital birth defects, intellectual disability, and cancer. However, despite the understanding of the fundamental mechanisms that control the SAC, it remains unknown how signaling pathways directly interact with and regulate the mitotic checkpoint activity. Read More

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Emerging Roles of Small GTPases in Islet β-Cell Function.

Cells 2021 Jun 15;10(6). Epub 2021 Jun 15.

Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.

Several small guanosine triphosphatases (GTPases) from the Ras protein superfamily regulate glucose-stimulated insulin secretion in the pancreatic islet β-cell. The Rho family GTPases Cdc42 and Rac1 are primarily involved in relaying key signals in several cellular functions, including vesicle trafficking, plasma membrane homeostasis, and cytoskeletal dynamics. They orchestrate specific changes at each spatiotemporal region within the β-cell by coordinating with signal transducers, guanine nucleotide exchange factors (GEFs), GTPase-activating factors (GAPs), and their effectors. Read More

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Identification of RHOBTB2 aberration as an independent prognostic indicator in acute myeloid leukemia.

Aging (Albany NY) 2021 06 1;13(11):15269-15284. Epub 2021 Jun 1.

Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, Shandong Province, PR China.

Rho-related BTB domain (RhoBTB) proteins belong to Rho guanosine triphosphatases (GTPases). Their putative role implicated in carcinogenesis has been supported by accumulating evidence. However, their expression pattern and potential role in acute myeloid leukemia (AML) remain unclear. Read More

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The RAL signaling network: Cancer and beyond.

Int Rev Cell Mol Biol 2021 2;361:21-105. Epub 2020 Dec 2.

Institute of Molecular Tumor Biology, Faculty of Medicine, University of Münster, Münster, Germany. Electronic address:

The RAL proteins RALA and RALB belong to the superfamily of small RAS-like GTPases (guanosine triphosphatases). RAL GTPases function as molecular switches in cells by cycling through GDP- and GTP-bound states, a process which is regulated by several guanine exchange factors (GEFs) and two heterodimeric GTPase activating proteins (GAPs). Since their discovery in the 1980s, RALA and RALB have been established to exert isoform-specific functions in central cellular processes such as exocytosis, endocytosis, actin organization and gene expression. Read More

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December 2020

Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration.

Int J Mol Sci 2021 Apr 23;22(9). Epub 2021 Apr 23.

Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, 48940 Leioa, Spain.

Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Read More

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Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration.

Sci Adv 2021 Apr 2;7(14). Epub 2021 Apr 2.

Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong 999077, China.

Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. Read More

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Plant Rho GTPase signaling promotes autophagy.

Mol Plant 2021 Jun 29;14(6):905-920. Epub 2021 Mar 29.

School of Life Sciences, Centre for Cell and Developmental Biology and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; Institute of Plant Molecular Biology and Agricultural Biotechnology, CUHK, Hong Kong, China; CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, N.T., Shenzhen, Hong Kong, 518057, China. Electronic address:

The roles of Rho family guanosine triphosphatases (GTPases) of plants (ROPs) in modulating plant growth and development have been well characterized. However, little is known about the roles of ROP signaling pathways in regulating plant autophagy and autophagosome formation. In this study, we identify a unique ROP signaling mechanism, which mediates developmental to autophagic transition under stress conditions in the model plant Arabidopsis. Read More

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When human guanylate-binding proteins meet viral infections.

J Biomed Sci 2021 Mar 5;28(1):17. Epub 2021 Mar 5.

Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.

Innate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. Read More

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Chemo-informatics guided study of natural inhibitors targeting rho GTPase: a lead for treatment of glaucoma.

In Silico Pharmacol 2021 3;9(1). Epub 2021 Jan 3.

Department of Biotechnology, Govind Ballabh Pant Institute of Engineering and Technology, Pauri Garhwal, Uttarakhand 246194 India.

Glaucoma, the most perilous disease leading to blindness is a result of optical neuropathy. Accumulation of aqueous humor in the posterior chamber due to a large difference in the rate of formation and its drainage in the anterior chamber causes an increase in intraocular pressure (IOP) leading to damage of nerve cells. A literature survey has revealed that inhibition of the Rho guanosine triphosphatases (rho GTPase) pathway by specific inhibitors leads to the relaxation of contractile cells involved in the aqueous outflow pathway. Read More

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January 2021

The PKGIα-Rac1 pathway is a novel regulator of insulin-dependent glucose uptake in cultured rat podocytes.

J Cell Physiol 2021 Jun 26;236(6):4655-4668. Epub 2020 Nov 26.

Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Gdańsk, Poland.

Insulin plays a major role in regulating glucose homeostasis in podocytes. Protein kinase G type Iα (PKGIα) plays an important role in regulating glucose uptake in these cells. Rac1 signaling plays an essential role in the reorganization of the actin cytoskeleton and is also essential for insulin-stimulated glucose transport. Read More

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TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer.

Front Pharmacol 2020 29;11:581455. Epub 2020 Sep 29.

Laboratoire de Cell Physiology, Université de Lille, Department of Life Sciences, Univ. Lille, Inserm, U1003-PHYCEL, Lille, France.

Transient Receptor Potential (TRP) cations channels, as key regulators of intracellular calcium homeostasis, play a central role in the essential hallmarks of cancer. Among the multiple pathways in which TRPs may be involved, here we focus our attention on the ones involving small guanosine triphosphatases (GTPases), summarizing the main processes associated with the metastatic cascade, such as migration, invasion and tumor vascularization. In the last decade, several studies have highlighted a bidirectional interplay between TRPs and small GTPases in cancer progression: TRP channels may affect small GTPases activity both Ca-dependent or Ca-independent pathways, and, conversely, some small GTPases may affect TRP channels activity through the regulation of their intracellular trafficking to the plasma membrane or acting directly on channel gating. Read More

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September 2020

Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense.

Science 2020 10;370(6514)

Cell Compartments and Signaling Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036, Barcelona, Spain.

Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. Read More

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October 2020

RASSF effectors couple diverse RAS subfamily GTPases to the Hippo pathway.

Sci Signal 2020 10 13;13(653). Epub 2020 Oct 13.

Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec H3T 1J4, Canada.

Small guanosine triphosphatases (GTPases) of the RAS superfamily signal by directly binding to multiple downstream effector proteins. Effectors are defined by a folded RAS-association (RA) domain that binds exclusively to GTP-loaded (activated) RAS, but the binding specificities of most RA domains toward more than 160 RAS superfamily GTPases have not been characterized. Ten RA domain family (RASSF) proteins comprise the largest group of related effectors and are proposed to couple RAS to the proapoptotic Hippo pathway. Read More

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October 2020

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases.

Int J Mol Sci 2020 Aug 31;21(17). Epub 2020 Aug 31.

Achucarro Basque Center for Neuroscience, Science Park of the Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), 48940 Leioa, Spain.

Small guanosine triphosphatases (GTPases) of the Ras superfamily are key regulators of many key cellular events such as proliferation, differentiation, cell cycle regulation, migration, or apoptosis. To control these biological responses, GTPases activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in some small GTPases also guanine nucleotide dissociation inhibitors (GDIs). Moreover, small GTPases transduce signals by their downstream effector molecules. Read More

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Rho GTPases in cancer radiotherapy and metastasis.

Cancer Metastasis Rev 2020 12 8;39(4):1245-1262. Epub 2020 Aug 8.

Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, China.

Despite treatment advances, radioresistance and metastasis markedly impair the benefits of radiotherapy to patients with malignancies. Functioning as molecular switches, Rho guanosine triphosphatases (GTPases) have well-recognized roles in regulating various downstream signaling pathways in a wide range of cancers. In recent years, accumulating evidence indicates the involvement of Rho GTPases in cancer radiotherapeutic efficacy and metastasis, as well as radiation-induced metastasis. Read More

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December 2020

The dynamic structure of Rab35 is stabilized in the presence of GTP under physiological conditions.

Biochem Biophys Rep 2020 Sep 24;23:100776. Epub 2020 Jun 24.

Faculty of Pharma-Science, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.

Rab proteins, a family of small guanosine triphosphatases, play key roles in intracellular membrane trafficking and the regulation of various cellular processes. As a Rab isoform, Rab35 is crucial for recycling endosome trafficking, cytokinesis and neurite outgrowth. In this report, we analyzed dynamic structural changes and physicochemical features of Rab35 in response to different external conditions, including temperature, pH, salt concentration and guanosine triphosphate (GTP), by circular dichroism (CD) spectroscopy. Read More

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September 2020

GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovarian Insufficiency Syndrome.

Ann Neurol 2020 08 18;88(2):332-347. Epub 2020 Jun 18.

Botnar Research Centre, National Institute for Health Research Biomedical Research Centre Oxford, University of Oxford, Oxford, United Kingdom.

Objective: A hitherto undescribed phenotype of early onset muscular dystrophy associated with sensorineural hearing loss and primary ovarian insufficiency was initially identified in 2 siblings and in subsequent patients with a similar constellation of findings. The goal of this study was to understand the genetic and molecular etiology of this condition.

Methods: We applied whole exome sequencing (WES) superimposed on shared haplotype regions to identify the initial biallelic variants in GGPS1 followed by GGPS1 Sanger sequencing or WES in 5 additional families with the same phenotype. Read More

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RhoJ Regulates α5β1 Integrin Trafficking to Control Fibronectin Remodeling during Angiogenesis.

Curr Biol 2020 06 16;30(11):2146-2155.e5. Epub 2020 Apr 16.

School of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK. Electronic address:

Rho guanosine triphosphatases (GTPases) are master regulators of cell shape and cell movement [1]. The archetypal family members RhoA, Rac1, and Cdc42 arose early in eukaryotic evolution and coordinate a diverse range of cell morphologies and migrations. Evolution of the vertebrates was paralleled by expansion of this family through gene duplication. Read More

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Comprehensive Analysis of the Expression and Prognosis for GBPs in Head and neck squamous cell carcinoma.

Sci Rep 2020 04 8;10(1):6085. Epub 2020 Apr 8.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Guanylate binding proteins (GBPs) belongs to the interferons (IFNs) induced guanylate-binding protein family (Guanosine triphosphatases, GTPases) consisting of seven homologous members, termed GBP1 to GBP7. We used multidimensional survey ways to explore GBPs expression, regulation, mutations, immune infiltration and functional networks in head and neck squamous cell carcinoma (HNSCC) patient data based on various open databases. The study provides staggered evidence for the significance of GBPs in HNSCC and its potential role as a novel biomarker. Read More

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Biochemical characterization of bacterial FeoBs: A perspective on nucleotide specificity.

Arch Biochem Biophys 2020 05 24;685:108350. Epub 2020 Mar 24.

Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, Republic of Korea. Electronic address:

Iron is an essential requirement for the survival and virulence of most bacteria. The bacterial ferrous iron transporter protein FeoB functions as a major reduced iron transporter in prokaryotes, but its biochemical mechanism has not been fully elucidated. In the present study, we compared enzymatic properties of the cytosolic portions of pathogenic bacterial FeoBs to elucidate each bacterial strain-specific characteristic of the Feo system. Read More

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Targeting and signaling of Rho of plants guanosine triphosphatases require synergistic interaction between guanine nucleotide inhibitor and vesicular trafficking.

J Integr Plant Biol 2020 Oct 16;62(10):1484-1499. Epub 2020 Apr 16.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, China.

Most eukaryotic cells are polarized. Common toolbox regulating cell polarization includes Rho guanosine triphosphatases (GTPases), in which spatiotemporal activation is regulated by a plethora of regulators. Rho of plants (ROPs) are the only Rho GTPases in plants. Read More

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October 2020

Rap1-GTPases control mTORC1 activity by coordinating lysosome organization with amino acid availability.

Nat Commun 2020 03 17;11(1):1416. Epub 2020 Mar 17.

Weill Cornell Medicine, Sandra and Edward Meyer Cancer Center, Belfer Research Building, 413 E. 69th St., New York, NY, 10021, USA.

The kinase mTOR complex 1 (mTORC1) promotes cellular growth and is frequently dysregulated in cancers. In response to nutrients, mTORC1 is activated on lysosomes by Rag and Rheb guanosine triphosphatases (GTPases) and drives biosynthetic processes. How limitations in nutrients suppress mTORC1 activity remains poorly understood. Read More

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Mitochondrial Dynamic Dysfunction as a Main Triggering Factor for Inflammation Associated Chronic Non-Communicable Diseases.

J Inflamm Res 2020 14;13:97-107. Epub 2020 Feb 14.

National Reference Laboratory for Clinical Chemistry, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.

Mitochondria are organelles with highly dynamic ultrastructure maintained by flexible fusion and fission rates governed by Guanosine Triphosphatases (GTPases) dependent proteins. Balanced control of mitochondrial quality control is crucial for maintaining cellular energy and metabolic homeostasis; however, dysfunction of the dynamics of fusion and fission causes loss of integrity and functions with the accumulation of damaged mitochondria and mitochondrial deoxyribose nucleic acid (mtDNA) that can halt energy production and induce oxidative stress. Mitochondrial derived reactive oxygen species (ROS) can mediate redox signaling or, in excess, causing activation of inflammatory proteins and further exacerbate mitochondrial deterioration and oxidative stress. Read More

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February 2020

The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways.

Biochem Res Int 2020 11;2020:4186308. Epub 2020 Feb 11.

Department of Orthopedics, Peking University Third Hospital, 49 North Garden Rd., Haidian District, Beijing 100191, China.

Ras analog in brain (Rab) proteins are small guanosine triphosphatases (GTPases) that belong to the Ras-like GTPase superfamily, and they can regulate vesicle trafficking. Rab proteins alternate between an activated (GTP-bound) state and an inactivated (GDP-bound) state. Early endosome marker Rab5 GTPase, a key member of the Rab family, plays a crucial role in endocytosis and membrane transport. Read More

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February 2020

Regulation of Small GTPase Prenylation in the Nervous System.

Mol Neurobiol 2020 May 27;57(5):2220-2231. Epub 2020 Jan 27.

Texas Woman's University, Denton, TX, USA.

Mevalonate pathway inhibitors have been extensively studied for their roles in cholesterol depletion and for inhibiting the prenylation and activation of various proteins. Inhibition of protein prenylation has potential therapeutic uses against neurological disorders, like neural cancers, neurodegeneration, and neurotramatic lesions. Protection against neurodegeneration and promotion of neuronal regeneration is regulated in large part by Ras superfamily small guanosine triphosphatases (GTPases), particularly the Ras, Rho, and Rab subfamilies. Read More

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Change of Ras and its guanosine triphosphatases (GTPases) during development and regression in bovine corpus luteum.

S H Lee S Lee

Theriogenology 2020 Mar 23;144:16-26. Epub 2019 Dec 23.

College of Animal Life Sciences, Kangwon National University, Chuncheon, Republic of Korea. Electronic address:

The aim of this study was to determine the change of Ras and its guanosine triphosphatases (GTPases) proteins in the bovine corpus luteum (CL) during estrous cycle and investigate protein-protein interaction between hormone receptors and Ras proteins via angiogenetic and apoptotic factors using bioinformatics database. The bovine CLs at proliferation phase (PP), secretion phase (SP), and regression phase (RP) were dissected from abattoir ovaries (n = 4/stage), whole of the tissue samples was used to analyze two-dimensional electrophoresis (2-DE), mRNA, and protein analysis. The protein-protein interaction between the Ras GTPases proteins and hormone receptors were analyzed using Search Tool for the Retrieval of Interacting Genes (STRING) database. Read More

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In Vitro Reconstitution Assays of Microtubule Amplification and Lattice Repair by the Microtubule-Severing Enzymes Katanin and Spastin.

Methods Mol Biol 2020 ;2101:27-38

Cell Biology and Biophysics Unit, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

Microtubules are non-covalent dynamic polymers essential for the life of all eukaryotic cells. Their dynamic behavior is regulated by a large array of cellular effectors. In vitro microtubule assays have been instrumental in dissecting the mechanism of microtubule-associated proteins. Read More

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January 2021

Biochemical and structural characterization of murine GBP7, a guanylate binding protein with an elongated C-terminal tail.

Biochem J 2019 11;476(21):3161-3182

Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Duesseldorf, Germany.

Guanylate-binding proteins (GBPs) constitute a family of interferon-inducible guanosine triphosphatases (GTPases) that are key players in host defense against intracellular pathogens ranging from protozoa to bacteria and viruses. So far, human GBP1 and GBP5 as well as murine GBP2 (mGBP2) have been biochemically characterized in detail. Here, with murine GBP7 (mGBP7), a GBP family member with an unconventional and elongated C-terminus is analyzed. Read More

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November 2019