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The Rho GTPases — RHOA, RAC1 and CDC42 — are small GTP binding proteins that regulate basic biological processes such as cell locomotion, cell division and morphogenesis by promoting cytoskeleton-based changes in the cell cortex. This regulation results from active (GTP-bound) Rho GTPases stimulating target proteins that, in turn, promote actin assembly and myosin 2-based contraction to organize the cortex. This basic regulatory scheme, well supported by in vitro studies, led to the natural assumption that Rho GTPases function in vivo in an essentially linear matter, with a given process being initiated by GTPase activation and terminated by GTPase inactivation. However, a growing body of evidence based on live cell imaging, modelling and experimental manipulation indicates that Rho GTPase activation and inactivation are often tightly coupled in space and time via signalling circuits and networks based on positive and negative feedback. In this Review, we present and discuss this evidence, and we address one of the fundamental consequences of coupled activation and inactivation: the ability of the Rho GTPases to self-organize, that is, direct their own transition from states of low order to states of high order. We discuss how Rho GTPase self-organization results in the formation of diverse spatiotemporal cortical patterns such as static clusters, oscillatory pulses, travelling wave trains and ring-like waves. Finally, we discuss the advantages of Rho GTPase self-organization and pattern formation for cell function.

2023 SEP 11 (NewsRx) -- By a News Reporter-Staff News Editor at Stem Cell Week -- Investigators discuss new findings in Science. According to news originating from Berkeley, California, by [...]

ABSTRACTRhoA, Rac1 and CDC42 are small G proteins that play a crucial role in regulating various cellular processes, such as the formation of actin cytoskeleton, cell shape and cell migration. Our recent results suggest that MLL is responsible for maintaining the balance of these small Rho GTPases. MLL depletion affects the stability of Rho GTPases, leading to a decrease in their protein levels and loss of activity. These changes manifest in the form of abnormal cell shape and disrupted actin cytoskeleton, resulting in reduced cell spreading and migration. Interestingly, their chaperone protein RhoGDI1 but not the Rho GTPases, is under the direct transcriptional regulation of MLL. Here, we comment on the possible implications of these observations on the signalling by Rho GTPases protein network.

2023 JUN 17 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Fresh data on Hypertrophy are presented in a new report. According to [...]

2023 JUN 17 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting based on a preprint abstract, our journalists obtained [...]

2023 MAR 25 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A new study on pharmacology is now available. According to news reporting [...]

2022 SEP 17 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Researchers detail new data in Genomics and Genetics. According to news reporting [...]

2022 JUL 16 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Data detailed on Cardiovascular Diseases and Conditions - Arteriosclerosis Thrombosis and Vascular [...]

Growing evidence suggests that Rho GTPases and molecules involved in their signaling pathways play a major role in the development of the central nervous system (CNS). Whole exome sequencing (WES) and de novo examination of mutations, including SNP (Single Nucleotide Polymorphism) in genes coding for the molecules of their signaling cascade, has allowed the recent discovery of dominant autosomic mutations and duplication or deletion of candidates in the field of neurodevelopmental diseases (NDD). Epidemiological studies show that the co-occurrence of several of these neurological pathologies may indeed be the rule. The regulators of Rho GTPases have often been considered for cognitive diseases such as intellectual disability (ID) and autism. But, in a remarkable way, mild to severe motor symptoms are now reported in autism and other cognitive NDD. Although a more abundant litterature reports the involvement of Rho GTPases and signaling partners in cognitive development, molecular investigations on their roles in central nervous system (CNS) development or degenerative CNS pathologies also reveal their role in embryonic and perinatal motor wiring through axon guidance and later in synaptic plasticity. Thus, Rho family small GTPases have been revealed to play a key role in brain functions including learning and memory but their precise role in motor development and associated symptoms in NDD has been poorly scoped so far, despite increasing clinical data highlighting the links between cognition and motor development. Indeed, early impairements in fine or gross motor performance is often an associated feature of NDDs, which then impact social communication, cognition, emotion, and behavior. We review here recent insights derived from clinical developmental neurobiology in the field of Rho GTPases and NDD (autism spectrum related disorder (ASD), ID, schizophrenia, hypotonia, spastic paraplegia, bipolar disorder and dyslexia), with a specific focus on genetic alterations affecting Rho GTPases that are involved in motor circuit development.

2022 MAY 14 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Data detailed on cancer have been presented. According to news reporting out [...]

ABSTRACTRho family GTPases are molecular switches best known for their pivotal role in dynamic regulation of the actin cytoskeleton, but also of cellular morphology, motility, adhesion and proliferation. The prototypic members of this family (RhoA, Rac1 and Cdc42) also contribute to the normal kidney function and play important roles in the structure and function of various kidney cells including tubular epithelial cells, mesangial cells and podocytes. The kidney’s vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally actin-based cytoskeleton podocyte forms the final cellular barrier to filtration. The glomerulus appears as a highly dynamic signalling hub that is capable of integrating intracellular cues from its individual structural components. Dynamic regulation of the podocyte cytoskeleton is required for efficient barrier function of the kidney. As master regulators of actin cytoskeletal dynamics, Rho GTPases are therefore of critical importance for sustained kidney barrier function. Dysregulated activities of the Rho GTPases and of their effectors are implicated in the pathogenesis of both hereditary and idiopathic forms of kidney diseases. Diabetic nephropathy is a progressive kidney disease that is caused by injury to kidney glomeruli. High glucose activates RhoA/Rho-kinase in mesangial cells, leading to excessive extracellular matrix production (glomerulosclerosis). This RhoA/Rho-kinase pathway also seems involved in the post-transplant hypertension frequently observed during treatment with calcineurin inhibitors, whereas Rac1 activation was observed in post-transplant ischaemic acute kidney injury.

ABSTRACTCytokinesis is required to cleave the daughter cells at the end of mitosis and relies on the spatiotemporal control of RhoA GTPase. Cytokinesis failure can lead to changes in cell fate or aneuploidy, which can be detrimental during development and/or can lead to cancer. However, our knowledge of the pathways that regulate RhoA during cytokinesis is limited, and the role of other Rho family GTPases is not clear. This is largely because the study of Rho GTPases presents unique challenges using traditional cell biological and biochemical methods, and they have pleiotropic functions making genetic studies difficult to interpret. The recent generation of optogenetic tools and biosensors that control and detect active Rho has overcome some of these challenges and is helping to elucidate the role of RhoA in cytokinesis. However, improvements are needed to reveal the role of other Rho GTPases in cytokinesis, and to identify the molecular mechanisms that control Rho activity. This review examines some of the outstanding questions in cytokinesis, and explores tools for the imaging and control of Rho GTPases.

A recent study investigated the effects of Streptococcus pneumoniae infection on lung epithelial cells. The study found that the bacteria's toxin, pneumolysin, caused a reduction in the expression of CD73, a protein involved in inflammation modulation. Additionally, the toxin led to the internalization of glycosylphosphatidylinositol anchored proteins (GPI-APs) through the activation of host Rho GTPases. This internalization process may serve as a rapid innate repair response to cell damage induced by the toxin. The findings suggest that this mechanism could help bacteria evade host defenses. However, it is important to note that this study has not yet undergone peer review. [Extracted from the article]

2021 APR 24 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- New research on vascular diseases and conditions is the subject of a [...]

2021 JAN 23 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators discuss new findings in cell biology. According to news reporting out [...]

2021 JAN 9 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Current study results on Oncology - Breast Cancer have been published. According [...]

2020 NOV 28 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Research findings on membrane transport proteins are discussed in a new report. [...]

2020 NOV 7 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators publish new report on Cardiovascular Diseases and Conditions - Thrombosis. According [...]

2020 NOV 7 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting based on a preprint abstract, our journalists obtained [...]

2020 OCT 17 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Researchers detail new data in breast cancer. According to news reporting from [...]

ABSTRACTA growing body of evidence implicates requisite roles for GTP and its binding proteins (Rho GTPases) in the cascade of events leading to physiological insulin secretion from the islet beta cell. Interestingly, chronic exposure of these cells to hyperglycaemic conditions appears to result in sustained activation of specific Rho GTPases (e.g. Rac1) leading to significant alterations in cellular functions including defects in mitochondrial function and nuclear collapse culminating in beta cell demise. One of the objectives of this review is to highlight our current understanding of the regulatory roles of GTP and Rho GTPases in normal islet function (e.g. proliferation and insulin secretion) as well potential defects in these signalling molecules and metabolic pathways that could contribute islet beta cell dysfunction and loss of functional beta cell mass leading to the onset of diabetes. Potential knowledge gaps in this field and possible avenues for future research are also highlighted.Abbreviations:ARNO: ADP-ribosylation factor nucleotide binding site opener; CML: carboxyl methylation; Epac: exchange protein directly activated by cAMP; ER stress: endoplasmic reticulum stress; FTase: farnesyltransferase; GAP: GTPase activating protein; GDI: GDP dissociation inhibitor; GEF: guanine nucleotide exchange factor; GGTase: geranylgeranyltransferase; GGpp: geranylgeranylpyrophosphate; GGPPS: geranylgeranyl pyrophosphate synthase; GSIS: glucose-stimulated insulin secretion; HGPRTase: hypoxanthine-guanine phosphoribosyltransferase; IMPDH: inosine monophosphate dehydrogenase; α-KIC: α-ketoisocaproic acid; MPA: mycophenolic acid; MVA: mevalonic acid; NDPK: nucleoside diphosphate kinase; NMPK: nucleoside monophosphate kinase; Nox2: phagocyte-like NADPH oxidase; PAK-I: p21-activated kinase-I; β-PIX: β-Pak-interacting exchange factor; PRMT: protein arginine methyltransferase; Rac1: ras-related C3 botulinum toxin substrate 1; Tiam1: T-cell lymphoma invasion and metastasis-inducing protein 1; Trx-1: thioredoxin-1; Vav2: vav guanine nucleotide exchange factor 2

ABSTRACTRho 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. Given the central location of this organelle, and the numerous membrane trafficking pathways that connect it to both the endocytic and secretory systems of cells, it is clear that the Golgi is fundamental for maintaining cellular homoeostasis. In this review, we describe these GTPases in the context of how they regulate Golgi architecture, membrane trafficking into and away from this organelle, and cell polarity and migration. We summarize the key findings that show the growing importance of the pool of Rho GTPases associated with Golgi function, namely Cdc42, RhoA, RhoD, RhoBTB1 and RhoBTB3, and we discuss how they act in concert with other key families of molecules associated with the Golgi, including Rab GTPases and matrix proteins.

2020 SEP 12 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Current study results on RNA Viruses - Coronavirus have been published. According [...]

2020 AUG 29 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Current study results on Cancer have been published. According to news reporting [...]

2020 MAY 30 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Fresh data on cancer are presented in a new report. According to [...]

2020 MAR 28 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A new study on Oncology - Prostate Cancer is now available. According [...]

2020 FEB 1 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators publish new report on Cell Biology. According to news reporting out [...]

Pathological bone loss diseases (osteolysis, Paget’s diseases) are commonly caused by the excessive differentiation and activity of osteoclasts. The Rho GTPases family members Rac1/2 (Rac1 and Rac2) have been reported for their special role in exerting multiple cellular functions during osteoclastic differentiation, which includes the most prominent function on dynamic actin cytoskeleton rearranging. Besides that, the increasing studies demonstrated that the regulating effects of Rac1/2 on the osteoclastic cytoskeletal organization are through the GEFs member Dock5. Although the amount of relevant studies on this topic is still limited, several excellent studies have been reported that extensively explored the molecular mechanisms involved in Rac1/2 and Dock5 during the osteoclastogenesis regulation, as well as their role as the therapeutic target in bone loss diseases. Herein, in this review, we aim to focus on recent advances studies for extensively understanding the role of Rho GTPases Rac1/2 and Dock5 in osteoclastogenesis, as well as their role as a potential therapeutic target in regulating osteoclastogenesis.

Damaged cells develop distinct patterns of Rho GTPases in their cortex around the wound. We find that dramatic changes in GTPase patterns ensue following very modest manipulations of GTPase activity. Computational modeling explains some, but not all of the observed patterning changes.

Ras homology (RHO) GTPases are signalling proteins that have crucial roles in triggering multiple immune functions. Through their interactions with a broad range of effectors and kinases, they regulate cytoskeletal dynamics, cell polarity and the trafficking and proliferation of immune cells. The activity and localization of RHO GTPases are highly controlled by classical families of regulators that share consensus motifs. In this Review, we describe the recent discovery of atypical modulators and partners of RHO GTPases, which bring an additional layer of regulation and plasticity to the control of RHO GTPase activities in the immune system. Furthermore, the development of large-scale genetic screening has now enabled researchers to identify dysregulation of RHO GTPase signalling pathways as a cause of many immune system-related diseases. We discuss the mutations that have been identified in RHO GTPases and their signalling circuits in patients with rare diseases. The discoveries of new RHO GTPase partners and genetic mutations in RHO GTPase signalling hubs have uncovered unsuspected layers of crosstalk with other signalling pathways and may provide novel therapeutic opportunities for patients affected by complex immune or broader syndromes.

ABSTRACTOncogenic protein kinase C epsilon (PKCε) promotes the formation of membrane ruffles and motility in non-small cell lung cancer (NSCLC) cells. We found that PKCε is down-regulated when NSCLC cells undergo epithelial-to-mesenchymal transition (EMT) in response to TGF-β, thus becoming dispensable for migration and invasion in the mesenchymal state. PKCε silencing or inhibition leads to stress fibre formation, suggesting that this kinase negatively regulates RhoA activity. Ruffle formation induced by PKCε activation in the epithelial state is dependent on PI3K, but does not involve the PI3K-dependent Rac-GEFs Ect2, Trio, Vav2 or Tiam1, suggesting alternative Rac-GEFs as mediators of this response. In the proposed model, PKCε acts as a rheostat for Rho GTPases that differs in the epithelial and mesenchymal states.

ABSTRACTMegakaryocytes (MKs) are the bone marrow (BM) cells that generate blood platelets by a process that requires: i) polyploidization responsible for the increased MK size and ii) cytoplasmic organization leading to extension of long pseudopods, called proplatelets, through the endothelial barrier to allow platelet release into blood. Low level of localized RHOA activation prevents actomyosin accumulation at the cleavage furrow and participates in MK polyploidization. In the platelet production, RHOA and CDC42 play opposite, but complementary roles. RHOA inhibits both proplatelet formation and MK exit from BM, whereas CDC42 drives the development of the demarcation membranes and MK migration in BM. Moreover, the RhoAor Cdc42MK specific knock-out in mice and the genetic alterations in their down-stream effectors in human induce a thrombocytopenia demonstrating their key roles in platelet production. A better knowledge of Rho-GTPase signalling is thus necessary to develop therapies for diseases associated with platelet production defects.Abbreviations:AKT: Protein Kinase BARHGEF2: Rho/Rac Guanine Nucleotide Exchange Factor 2ARP2/3: Actin related protein 2/3BM: Bone marrowCDC42: Cell division control protein 42 homologCFU-MK: Colony-forming-unit megakaryocyteCIP4: Cdc42-interacting protein 4mDIA: DiaphanousDIAPH1; Protein diaphanous homolog 1ECT2: Epithelial Cell Transforming Sequence 2FLNA: Filamin AGAP: GTPase-activating proteins or GTPase-accelerating proteinsGDI: GDP Dissociation InhibitorGEF: Guanine nucleotide exchange factorHDAC: Histone deacetylaseLIMK: LIM KinaseMAL: Megakaryoblastic leukaemiaMARCKS: Myristoylated alanine-rich C-kinase substrateMKL: Megakaryoblastic leukaemiaMLC: Myosin light chainMRTF: Myocardin Related Transcription FactorOTT: One-Twenty Two ProteinPACSIN2: Protein Kinase C And Casein Kinase Substrate In Neurons 2PAK: P21-Activated KinasePDK: Pyruvate Dehydrogenase kinasePI3K: Phosphoinositide 3-kinasePKC: Protein kinase CPTPRJ: Protein tyrosine phosphatase receptor type JRAC: Ras-related C3 botulinum toxin substrate 1RBM15: RNA Binding Motif Protein 15RHO: Ras homologousROCK: Rho-associated protein kinaseSCAR: Suppressor of cAMP receptorSRF: Serum response factorSRC: SarcTAZ: Transcriptional coactivator with PDZ motifTUBB1: Tubulin β1VEGF: Vascular endothelial growth factorWAS: Wiskott Aldrich syndromeWASP: Wiskott Aldrich syndrome proteinWAVE: WASP-family verprolin-homologous proteinWIP: WASP-interacting proteinYAP: Yes-associated protein

2019 SEP 28 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- New research on Cell Biology is the subject of a report. According [...]

2019 AUG 3 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Data detailed on Molecular Research have been presented. According to news reporting [...]

2019 FEB 9 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A new study on Cancer is now available. According to news originating [...]

ABSTRACTThe Rho GTPases were discovered more than 30 years ago, and they were for a long time considered to follow simple cycling between GDP-bound and GTP-bound conformations, as for the Ras subfamily of small GTPases. The Rho GTPases consist of 20 members, but at least 10 of these do not follow this classical GTPase cycle. Thus, based on their kinetic properties, these Rho GTPases can instead be classified as atypical. Some of these atypical Rho GTPases do not hydrolyze GTP, and some have significantly increased intrinsic GDP/GTP exchange activity. This review focuses on this latter category of atypical Rho GTPases, the so-called ‘fast-cycling’ Rho GTPases. The different members of these fast-cycling atypical Rho GTPases are described in more detail here, along with their potential regulatory mechanisms. Finally, some insights are provided into the involvement of the atypical Rho GTPases in human pathologies.

The Rho GTPases RhoA, Rac1, and Cdc42 are important regulators of cytoskeletal dynamics. Although many in vitro and in vivo data indicate tumor-promoting effects of activated Rho GTPases, also tumor suppressive functions have been described, suggesting either highly cell-type-specific functions for Rho GTPases in cancer or insufficient cancer models. The availability of a large number of cancer genome-sequencing data by The Cancer Genome Atlas (TCGA) allows for the investigation of Rho GTPase function in human cancers in silico. This information should be used to improve our in vitro and in vivo cancer models, which are essential for a molecular understanding of Rho GTPase function in malignant tumors and for the potential development of cancer drugs targeting Rho GTPase signaling.

A recent study from Iowa State University explores the mechanisms involved in the specification of hematopoietic stem cells (HSCs), which could have implications for HSC transplantation and cellular immunotherapies. The researchers found that the early activation of the Nod1-Ripk2-NF-kB inflammatory pathway in endothelial cells (ECs) is crucial for the switch to definitive hemogenic endothelium and the specification of HSCs. The study suggests that manipulating this pathway could help generate functional patient-specific HSCs for the treatment of blood disorders. The research was published in Nature Communications and can be accessed for free through the provided link. [Extracted from the article]

For more information on this research see: Dahuang-Taoren, a botanical drug combination, ameliorates adenomyosis via inhibiting Rho GTPases. Keywords: Drugs and Therapies; Pharmacology EN Drugs and Therapies Pharmacology 709 709 1 03/23/23 20230324 NES 230324 2023 MAR 24 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- A new study on pharmacology is now available. [Extracted from the article]

2018 AUG 11 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Current study results on Chemistry - Biochemistry have been published. According to [...]

2018 JUN 9 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A new study on Gram-Negative Bacteria - Legionella pneumophila is now available. [...]

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Cytoskeletal reorganization driven by Rho GTPases plays a crucial role in the migration of T cells, which are key regulators of immunity. The molecular mechanisms that control actin cytoskeleton remodeling during T cell movement have only partially been clarified as the function of many modulators has not been evaluated in these cells. Here, we report a new function of RhoGDI2 by showing that this protein positively regulates Rho GTPase activation during T cell adhesion and migration. RhoGDI2 knockdown significantly reduced T cell adhesion and migration. Furthermore, RhoGDI2 knockdown decreased the activation of Rac1 and Cdc42, 2 members of Rho GTPases, and the remodeling of the actin cytoskeleton. Upon P‐selectin glycoprotein ligand‐1 engagement, RhoGDI2 was phosphorylated at Y24 and Y153 by kinases related to β2 integrin outside‐in signaling, Src, c‐Abl, and Syk, resulting in the accumulation of RhoGDI2 at the cell membrane. Subsequent phosphorylation of S31 induced the opening of RhoGDI2 and the release of Rho GTPases, whereas phosphorylation of Y153 might promote the activation of Rho GTPases by recruiting Vav1. Moreover, the disruption of lipid rafts with methyl‐β‐cyclodextrin blocked the interaction between integrins and RhoGDI2, reducing the level of phosphorylated RhoGDI2 and the activation of downstream Rho GTPases. Based on these observations, RhoGDI2 is a target of intergrin outside‐in signaling that activates Rho GTPases during T cell adhesion and migration, and RhoGDI2‐mediated signal transduction is based on the lipid rafts integrity. The kinases downstream of β2 integrin outside‐in signaling regulates RhoGDI2 phosphorylation to positively activate Rho GTPases in T cells adhesion and migration.

Supplemental Digital Content is available in the text.

Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.

ABSTRACTThe Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis. This provides insight into Arf regulation of the actin cytoskeleton, while putting the spotlight on small GTPase cooperation with emerging evidence of its importance in fundamental cell biology and interactions with pathogenic bacteria.

2017 AUG 5 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators publish new report on Oncology - Carcinomas. According to news reporting [...]