402 results match your criteria rho rab

Fibroblast activation protein inhibitor (FAPi) positive tumour fraction on PET/CT correlates with Ki-67 in liver metastases of neuroendocrine tumours.

Nuklearmedizin 2021 Jul 13. Epub 2021 Jul 13.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

Aim: Gallium-68-labelled inhibitors of the fibroblast activation protein (FAPi) enable positron emission tomography/computed tomography (PET/CT) imaging of fibroblast activation. We evaluated if [Ga]Ga-DATA5 m.SA. Read More

View Article and Full-Text PDF

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

View Article and Full-Text PDF

Active GTPase Pulldown Protocol.

Methods Mol Biol 2021 ;2262:117-135

Institute of Molecular Cell Biology, Center for Molecular Biomedicine, University Hospital Jena, Jena, Germany.

Ras and its related small GTPases are important signalling nodes that regulate a wide variety of cellular functions. The active form of these proteins exists in a transient GTP bound state that mediates downstream signalling events. The dysregulation of these GTPases has been associated with the progression of multiple diseases, most prominently cancer and developmental syndromes known as Rasopathies. Read More

View Article and Full-Text PDF

The Small GTPases in Fungal Signaling Conservation and Function.

Cells 2021 Apr 28;10(5). Epub 2021 Apr 28.

Laboratorio de Genómica Funcional y Comparativa, División de Biología Molecular, IPICYT, San Luis Potosí 78216, Mexico.

Monomeric GTPases, which belong to the Ras superfamily, are small proteins involved in many biological processes. They are fine-tuned regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Several families have been identified in organisms from different kingdoms. Read More

View Article and Full-Text PDF

DNA methylation variations in familial female and male breast cancer.

Oncol Lett 2021 Jun 12;21(6):468. Epub 2021 Apr 12.

Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, I-25123 Brescia, Italy.

In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level. Read More

View Article and Full-Text PDF

Stability Prediction for Mutations in the Cytosolic Domains of Cystic Fibrosis Transmembrane Conductance Regulator.

J Chem Inf Model 2021 04 15;61(4):1762-1777. Epub 2021 Mar 15.

Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel.

Cystic Fibrosis (CF) is caused by mutations to the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. CFTR is composed of two membrane spanning domains, two cytosolic nucleotide-binding domains (NBD1 and NBD2) and a largely unstructured R-domain. Multiple CF-causing mutations reside in the NBDs and some are known to compromise the stability of these domains. Read More

View Article and Full-Text PDF

Dietary Geranylgeranyl Pyrophosphate Counteracts the Benefits of Statin Therapy in Experimental Pulmonary Hypertension.

Circulation 2021 May 4;143(18):1775-1792. Epub 2021 Mar 4.

Department of Pathophysiology, School of Basic Medicine (L.Z., F.L., Q. Hao, T.F., Z.C., S.L., R.X., M.S., T.Z., X.F., X.Z., Q. Hu), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown. Read More

View Article and Full-Text PDF

Tuba Activates Cdc42 during Neuronal Polarization Downstream of the Small GTPase Rab8a.

J Neurosci 2021 02 21;41(8):1636-1649. Epub 2021 Jan 21.

Laboratory of Cell and Neuronal Dynamics, Department of Biology, Faculty of Sciences, Universidad de Chile, 7800003, Santiago, Chile

The acquisition of neuronal polarity is a complex molecular process that depends on changes in cytoskeletal dynamics and directed membrane traffic, regulated by the Rho and Rab families of small GTPases, respectively. However, during axon specification, a molecular link that couples these protein families has yet to be identified. In this paper, we describe a new positive feedback loop between Rab8a and Cdc42, coupled by Tuba, a Cdc42-specific guanine nucleotide-exchange factor (GEF), that ensures a single axon generation in rodent hippocampal neurons from embryos of either sex. Read More

View Article and Full-Text PDF
February 2021

Effects of 7,8-Dihydroxyflavone on Lipid Isoprenoid and Rho Protein Levels in Brains of Aged C57BL/6 Mice.

Neuromolecular Med 2021 03 30;23(1):130-139. Epub 2020 Dec 30.

Department of Pharmacology, Biocenter Niederursel, University of Frankfurt, Goethe-University, Max-von-Laue-St. 9, 60438, Frankfurt, Germany.

Synaptic impairment may be the main cause of cognitive dysfunction in brain aging that is probably due to a reduction in synaptic contact between the axonal buttons and dendritic spines. Rho proteins including the small GTPase Rac1 have become key regulators of neuronal morphogenesis that supports synaptic plasticity. Small Rho- and Ras-GTPases are post-translationally modified by the isoprenoids geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP), respectively. Read More

View Article and Full-Text PDF

Proteomic profiling of peripheral blood mononuclear cells isolated from patients with tuberculosis and diabetes copathogenesis - A pilot study.

PLoS One 2020 6;15(11):e0233326. Epub 2020 Nov 6.

Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background: Diabetes is an important risk factor for developing tuberculosis. This association leads to exacerbation of tuberculosis symptoms and delayed treatment of both the diseases. Molecular mechanism and biomarkers/drug targets related to copathogenesis of tuberculosis and diabetes are still poorly understood. Read More

View Article and Full-Text PDF
December 2020

LET-502/ROCK Regulates Endocytic Recycling by Promoting Activation of RAB-5 in a Distinct Subpopulation of Sorting Endosomes.

Cell Rep 2020 09;32(12):108173

Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China. Electronic address:

To explore the mechanism of Rab5/RAB-5 activation during endocytic recycling, we perform a genome-wide RNAi screen and identify a recycling regulator, LET-502/ROCK. LET-502 preferentially interacts with RAB-5(GDP) and activates RABX-5 GEF activity toward RAB-5, presumably by disrupting the self-inhibiting conformation of RABX-5. Furthermore, we find that the concomitant loss of LET-502 and another CED-10 effector, TBC-2/RAB-5-GAP, results in an endosomal buildup of RAB-5, indicating that CED-10 directs TBC-2-mediated RAB-5 inactivation and re-activates RAB-5 via LET-502 afterward. Read More

View Article and Full-Text PDF
September 2020

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology.

Mol Biol Cell 2020 11 17;31(23):2570-2582. Epub 2020 Sep 17.

Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.

Polarized growth requires the integration of polarity pathways with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake. In budding yeast, the myosin-V Myo2 is aided by the kinesin-related protein Smy1 in carrying out the essential Sec4-dependent transport of secretory vesicles to sites of polarized growth. Overexpression suppressors of a conditional mutant identified a novel F-BAR (Fes/CIP4 homology-Bin-Amphiphysin-Rvs protein)-containing RhoGAP, Rgd3, that has activity primarily on Rho3, but also Cdc42. Read More

View Article and Full-Text PDF
November 2020

Oncoprotein-specific molecular interaction maps (SigMaps) for cancer network analyses.

Nat Biotechnol 2021 02 14;39(2):215-224. Epub 2020 Sep 14.

Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.

Tumor-specific elucidation of physical and functional oncoprotein interactions could improve tumorigenic mechanism characterization and therapeutic response prediction. Current interaction models and pathways, however, lack context specificity and are not oncoprotein specific. We introduce SigMaps as context-specific networks, comprising modulators, effectors and cognate binding-partners of a specific oncoprotein. Read More

View Article and Full-Text PDF
February 2021

Emerging roles for Rho GTPases operating at the Golgi complex.

Small GTPases 2020 Sep 3:1-12. Epub 2020 Sep 3.

Cell Screening Laboratory, School of Biology & Environmental Science, University College Dublin (UCD), Dublin Ireland.

Rho GTPases are known to play an essential role in fundamental processes such as defining cell shape, polarity and migration. As such, the majority of Rho GTPases localize and function at, or close to, the plasma membrane. However, it is becoming increasingly clear that a number of Rho family proteins are also associated with the Golgi complex, where they not only regulate events at this organelle but also more widely across the cell. Read More

View Article and Full-Text PDF
September 2020

Uncovering Tumor-Stroma Inter-relationships Using MALDI Mass Spectrometry Imaging.

J Proteome Res 2020 10 16;19(10):4093-4103. Epub 2020 Sep 16.

Future Industries Institute, University of South Australia, Mawson Lakes SA 5095, Australia.

Tumorigenesis involves a complex interplay between genetically modified cancer cells and their adjacent normal tissue, the stroma. We used an established breast cancer mouse model to investigate this inter-relationship. Conditional activation of Rho-associated protein kinase (ROCK) in a model of mammary tumorigenesis enhances tumor growth and progression by educating the stroma and enhancing the production and remodeling of the extracellular matrix. Read More

View Article and Full-Text PDF
October 2020

The Rab GAP RN-tre cross-talks with the Rho1 signaling pathway to regulate nonmuscle myosin II localization and function.

Mol Biol Cell 2020 10 20;31(21):2379-2397. Epub 2020 Aug 20.

Department of Biology, Reed College, Portland, OR 97202.

To identify novel regulators of nonmuscle myosin II (NMII) we performed an image-based RNA interference screen using stable S2 cells expressing the enhanced green fluorescent protein (EGFP)-tagged regulatory light chain (RLC) of NMII and mCherry-Actin. We identified the Rab-specific GTPase-activating protein (GAP) RN-tre as necessary for the assembly of NMII RLC into contractile actin networks. Depletion of RN-tre led to a punctate NMII phenotype, similar to what is observed following depletion of proteins in the Rho1 pathway. Read More

View Article and Full-Text PDF
October 2020

Kalirin Interacts with TRAPP and Regulates Rab11 and Endosomal Recycling.

Cells 2020 05 4;9(5). Epub 2020 May 4.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Coordinated actions of Rab and Rho are necessary for numerous essential cellular processes ranging from vesicle budding to whole cell movement. How Rab and Rho are choreographed is poorly understood. Here, we report a protein complex comprised of kalirin, a Rho guanine nucleotide exchange factor (GEF) activating Rac1, and RabGEF transport protein particle (TRAPP). Read More

View Article and Full-Text PDF

RNA Interference Screening Identifies Novel Roles for RhoBTB1 and RhoBTB3 in Membrane Trafficking Events in Mammalian Cells.

Cells 2020 04 28;9(5). Epub 2020 Apr 28.

Cell Screening Laboratory, School of Biology and Environmental Science & Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.

In the endomembrane system of mammalian cells, membrane traffic processes require a high degree of regulation in order to ensure their specificity. The range of molecules that participate in trafficking events is truly vast, and much attention to date has been given to the Rab family of small GTPases. However, in recent years, a role in membrane traffic for members of the Rho GTPase family, in particular Cdc42, has emerged. Read More

View Article and Full-Text PDF

Comparison of serum protein profiles between major depressive disorder and bipolar disorder.

BMC Psychiatry 2020 04 3;20(1):145. Epub 2020 Apr 3.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Background: Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. Read More

View Article and Full-Text PDF

Integrative structure and function of the yeast exocyst complex.

Protein Sci 2020 06 1;29(6):1486-1501. Epub 2020 May 1.

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.

Exocyst is an evolutionarily conserved hetero-octameric tethering complex that plays a variety of roles in membrane trafficking, including exocytosis, endocytosis, autophagy, cell polarization, cytokinesis, pathogen invasion, and metastasis. Exocyst serves as a platform for interactions between the Rab, Rho, and Ral small GTPases, SNARE proteins, and Sec1/Munc18 regulators that coordinate spatial and temporal fidelity of membrane fusion. However, its mechanism is poorly described at the molecular level. Read More

View Article and Full-Text PDF

Small GTPases: Structure, biological function and its interaction with nanoparticles.

Asian J Pharm Sci 2019 Jan 31;14(1):30-39. Epub 2018 Jul 31.

Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.

Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells. It plays an important role in cytoskeletal reorganization, cell polarity, cell cycle progression, gene expression and many other significant events in cells, such as the interaction with foreign particles. Therefore, it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay, since more and more nanomedicine are supposed to be used in biomedical field. Read More

View Article and Full-Text PDF
January 2019

Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.

Proc Natl Acad Sci U S A 2020 02 4;117(7):3627-3636. Epub 2020 Feb 4.

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226;

The chaperone protein SmgGDS promotes cell-cycle progression and tumorigenesis in human breast and nonsmall cell lung cancer. Splice variants of SmgGDS, named SmgGDS-607 and SmgGDS-558, facilitate the activation of oncogenic members of the Ras and Rho families of small GTPases through membrane trafficking via regulation of the prenylation pathway. SmgGDS-607 interacts with newly synthesized preprenylated small GTPases, while SmgGDS-558 interacts with prenylated small GTPases. Read More

View Article and Full-Text PDF
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

View Article and Full-Text PDF

Regulation of mTORC1 by Small GTPases in Response to Nutrients.

Min Zhu Xiu-Qi Wang

J Nutr 2020 05;150(5):1004-1011

College of Animal Science, South China Agricultural University/Guangdong Provincial Key Laboratory of Animal Nutrition Control/National Engineering Research Center for Breeding Swine Industry, Guangzhou, Guangdong, China.

Mechanistic target of rapamycin complex 1 (mTORC1) is a highly evolutionarily conserved serine/threonine kinase that regulates cell growth and metabolism in response to multiple environmental cues, such as nutrients, hormones, energy, and stress. Deregulation of mTORC1 can lead to diseases such as diabetes, obesity, and cancer. A series of small GTPases, including Rag, Ras homolog enriched in brain (Rheb), adenosine diphosphate ribosylation factor 1 (Arf1), Ras-related protein Ral-A, Ras homolog (Rho), and Rab, are involved in regulating mTORC1 in response to nutrients, and mTORC1 is differentially regulated via these small GTPases according to specific conditions. Read More

View Article and Full-Text PDF

PEBP1/RKIP behavior: a mirror of actin-membrane organization.

Cell Mol Life Sci 2020 Mar 20;77(5):859-874. Epub 2020 Jan 20.

UMR CNRS 7590, Museum National d'Histoire Naturelle, IRD, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, IMPMC, Sorbonne Université, 75005, Paris, France.

Phosphatidylethanolamine-binding protein 1 (PEBP1), a small 21 kDa protein, is implicated in several key processes of the living cell. The deregulation of PEBP1, especially its downregulation, leads to major diseases such as cancer and Alzheimer's disease. PEBP1 was found to interact with numerous proteins, especially kinases and GTPases, generally inhibiting their activity. Read More

View Article and Full-Text PDF

Exocyst structural changes associated with activation of tethering downstream of Rho/Cdc42 GTPases.

J Cell Biol 2020 02;219(2)

Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC.

The exocyst complex plays a critical role in determining both temporal and spatial dynamics of exocytic vesicle tethering and fusion with the plasma membrane. However, the mechanism by which the exocyst functions and how it is regulated remain poorly understood. Here we describe a novel biochemical assay for the examination of exocyst function in vesicle tethering. Read More

View Article and Full-Text PDF
February 2020

Autoactivation of small GTPases by the GEF-effector positive feedback modules.

F1000Res 2019 23;8. Epub 2019 Sep 23.

Centre for Synthetic and Systems Biology, Institute for Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK.

Small GTPases are organizers of a plethora of cellular processes. The time and place of their activation are tightly controlled by the localization and activation of their regulators, guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Remarkably, in some systems, the upstream regulators of GTPases are also found downstream of their activity. Read More

View Article and Full-Text PDF
October 2019

GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.

Yale J Biol Med 2019 09 20;92(3):453-470. Epub 2019 Sep 20.

Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, Yale University, New Haven, CT.

Fat and muscle cells contain a specialized, intracellular organelle known as the GLUT4 storage vesicle (GSV). Insulin stimulation mobilizes GSVs, so that these vesicles fuse at the cell surface and insert GLUT4 glucose transporters into the plasma membrane. This example is likely one instance of a broader paradigm for regulated, non-secretory exocytosis, in which intracellular vesicles are translocated in response to diverse extracellular stimuli. Read More

View Article and Full-Text PDF
September 2019

Water in Ras Superfamily Evolution.

J Comput Chem 2020 02 4;41(5):402-414. Epub 2019 Sep 4.

Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Ave, Boston, Massachusetts, 02115.

The Ras GTPase superfamily of proteins coordinates a diverse set of cellular outcomes, including cell morphology, vesicle transport, and cell proliferation. Primary amino acid sequence analysis has identified Specificity determinant positions (SDPs) that drive diversified functions specific to the Ras, Rho, Rab, and Arf subfamilies (Rojas et al. 2012, J Cell Biol 196:189-201). Read More

View Article and Full-Text PDF
February 2020

Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling.

J Cell Biochem 2020 02 26;121(2):1072-1086. Epub 2019 Aug 26.

Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Rab11 family interacting protein 2 (Rab11-FIP2) is a conserved protein and effector molecule for the small GTPase Rab11. By interacting with Rab11 and MYO5B, Rab11-FIP2 regulates endosome trafficking of plasma membrane proteins, promoting cellular motility. The endosomal trafficking system in nasopharyngeal carcinoma (NPC) remains unclear. Read More

View Article and Full-Text PDF
February 2020