scholarly journals Coordination between Rac1 and Rab Proteins: Functional Implications in Health and Disease

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 396 ◽  
Author(s):  
Margiotta ◽  
Bucci
Keyword(s):  
Reactive Oxygen Species ◽  
Small Gtpases ◽  
Actin Dynamics ◽  
Rab Proteins ◽  
Oxygen Species ◽  
Cellular Processes ◽  
Functional Implications ◽  
Health And Disease ◽  
Rho Family ◽  
Regulation Of Actin Cytoskeleton

The small GTPases of the Rho family regulate many aspects of actin dynamics, but are functionally connected to many other cellular processes. Rac1, a member of this family, besides its known function in the regulation of actin cytoskeleton, plays a key role in the production of reactive oxygen species, in gene transcription, in DNA repair, and also has been proven to have specific roles in neurons. This review focuses on the cooperation between Rac1 and Rab proteins, analyzing how the coordination between these GTPases impact on cells and how alterations of their functions lead to disease.

scholarly journals Rho-Family Small GTPases: From Highly Polarized Sensory Neurons to Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 92 ◽  
Author(s):  
Takehiko Ueyama
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Small Gtpases ◽  
In Vivo Studies ◽  
Signal Pathways ◽  
Ros Production ◽  
Oxygen Species ◽  
Rho Family Gtpases ◽  
Rho Family

The small GTPases of the Rho-family (Rho-family GTPases) have various physiological functions, including cytoskeletal regulation, cell polarity establishment, cell proliferation and motility, transcription, reactive oxygen species (ROS) production, and tumorigenesis. A relatively large number of downstream targets of Rho-family GTPases have been reported for in vitro studies. However, only a small number of signal pathways have been established at the in vivo level. Cumulative evidence for the functions of Rho-family GTPases has been reported for in vivo studies using genetically engineered mouse models. It was based on different cell- and tissue-specific conditional genes targeting mice. In this review, we introduce recent advances in in vivo studies, including human patient trials on Rho-family GTPases, focusing on highly polarized sensory organs, such as the cochlea, which is the primary hearing organ, host defenses involving reactive oxygen species (ROS) production, and tumorigenesis (especially associated with RAC, novel RAC1-GSPT1 signaling, RHOA, and RHOBTB2).

scholarly journals Reactive Oxygen Species: Beyond Their Reactive Behavior

2021 ◽  
Vol 46 (1) ◽  
pp. 77-87
Author(s):  
Arnaud Tauffenberger ◽  
Pierre J. Magistretti
Keyword(s):  
Reactive Oxygen Species ◽  
Second Messengers ◽  
Critical Role ◽  
Complex Function ◽  
Reactive Oxygen ◽  
High Reactivity ◽  
Oxygen Species ◽  
Health And Disease ◽  
Cellular Dysfunction ◽  
The Brain

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.

Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells

2002 ◽  
Vol 115 (9) ◽  
pp. 1837-1846 ◽  
Author(s):  
Sandra van Wetering ◽  
Jaap D. van Buul ◽  
Safira Quik ◽  
Frederik P. J. Mul ◽  
Eloise C. Anthony ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Reactive Oxygen ◽  
Small Gtpases ◽  
Endothelial Cell Migration ◽  
Oxygen Species ◽  
Cell Cell

The integrity of the endothelium is dependent on cell-cell adhesion, which is mediated by vascular-endothelial (VE)-cadherin. Proper VE-cadherin-mediated homotypic adhesion is, in turn, dependent on the connection between VE-cadherin and the cortical actin cytoskeleton. Rho-like small GTPases are key molecular switches that control cytoskeletal dynamics and cadherin function in epithelial as well as endothelial cells. We show here that a cell-penetrating, constitutively active form of Rac (Tat-RacV12) induces a rapid loss of VE-cadherin-mediated cell-cell adhesion in endothelial cells from primary human umbilical veins (pHUVEC). This effect is accompanied by the formation of actin stress fibers and is dependent on Rho activity. However,transduction of pHUVEC with Tat-RhoV14, which induces pronounced stress fiber and focal adhesion formation, did not result in a redistribution of VE-cadherin or an overall loss of cell-cell adhesion. In line with this observation, endothelial permeability was more efficiently increased by Tat-RacV12 than by Tat-RhoV14. The loss of cell-cell adhesion, which is induced by Tat-RacV12, occurred in parallel to and was dependent upon the intracellular production of reactive oxygen species (ROS). Moreover, Tat-RacV12 induced an increase in tyrosine phosphorylation of a component the VE-cadherin-catenin complex, which was identified as α-catenin. The functional relevance of this signaling pathway was further underscored by the observation that endothelial cell migration, which requires a transient reduction of cell-cell adhesion, was blocked when signaling through ROS was inhibited. In conclusion, Rac-mediated production of ROS represents a previously unrecognized means of regulating VE-cadherin function and may play an important role in the (patho)physiology associated with inflammation and endothelial damage as well as with endothelial cell migration and angiogenesis.

scholarly journals Polymerase-δ-interacting protein 2 activates the RhoGEF epithelial cell transforming sequence 2 in vascular smooth muscle cells

2019 ◽  
Vol 316 (5) ◽  
pp. C621-C631 ◽  
Author(s):  
Lauren Parker Huff ◽  
Daniel Seicho Kikuchi ◽  
Elizabeth Faidley ◽  
Steven J. Forrester ◽  
Michelle Z. Tsai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Smooth Muscle ◽  
Epithelial Cell ◽  
Vascular Smooth Muscle ◽  
Vascular Smooth Muscle Cells ◽  
Oxygen Species ◽  
Interacting Protein ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Cell Transforming

Polymerase-δ-interacting protein 2 (Poldip2) controls a wide variety of cellular functions and vascular pathologies. To mediate these effects, Poldip2 interacts with numerous proteins and generates reactive oxygen species via the enzyme NADPH oxidase 4 (Nox4). We have previously shown that Poldip2 can activate the Rho family GTPase RhoA, another signaling node within the cell. In this study, we aimed to better understand how Poldip2 activates Rho family GTPases and the functions of the involved proteins in vascular smooth muscle cells (VSMCs). RhoA is activated by guanine nucleotide exchange factors. Using nucleotide-free RhoA (isolated from bacteria) to pulldown active RhoGEFs, we found that the RhoGEF epithelial cell transforming sequence 2 (Ect2) is activated by Poldip2. Ect2 is a critical RhoGEF for Poldip2-mediated RhoA activation, because siRNA against Ect2 prevented Poldip2-mediated RhoA activity (measured by rhotekin pulldowns). Surprisingly, we were unable to detect a direct interaction between Poldip2 and Ect2, as they did not coimmunoprecipitate. Nox4 is not required for Poldip2-driven Ect2 activation, as Poldip2 overexpression induced Ect2 activation in Nox4 knockout VSMCs similar to wild-type cells. However, antioxidant treatment blocked Poldip2-induced Ect2 activation. This indicates a novel reactive oxygen species-driven mechanism by which Poldip2 regulates Rho family GTPases. Finally, we examined the function of these proteins in VSMCs, using siRNA against Poldip2 or Ect2 and determined that Poldip2 and Ect2 are both essential for vascular smooth muscle cell cytokinesis and proliferation.

scholarly journals Grit, a GTPase-Activating Protein for the Rho Family, Regulates Neurite Extension through Association with the TrkA Receptor and N-Shc and CrkL/Crk Adapter Molecules

2002 ◽  
Vol 22 (24) ◽  
pp. 8721-8734 ◽  
Author(s):  
Takeshi Nakamura ◽  
Misako Komiya ◽  
Kiyoaki Sone ◽  
Eiji Hirose ◽  
Noriko Gotoh ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Neuronal Cells ◽  
Small Gtpases ◽  
Actin Dynamics ◽  
Gtpase Activating Protein ◽  
Interacting Protein ◽  
High Affinity Receptor ◽  
Rho Family

ABSTRACT Neurotrophins are key regulators of the fate and shape of neuronal cells and act as guidance cues for growth cones by remodeling the actin cytoskeleton. Actin dynamics is controlled by Rho GTPases. We identified a novel Rho GTPase-activating protein (Grit) for Rho/Rac/Cdc42 small GTPases. Grit was abundant in neuronal cells and directly interacted with TrkA, a high-affinity receptor for nerve growth factor (NGF). Another pool of Grit was recruited to the activated receptor tyrosine kinase through its binding to N-Shc and CrkL/Crk, adapter molecules downstream of activated receptor tyrosine kinases. Overexpression of the TrkA-binding region of Grit inhibited NGF-induced neurite elongation. Further, we found some tendency for neurite promotion in full-length Grit-overexpressing PC12 cells upon NGF stimulation. These results suggest that Grit, a novel TrkA-interacting protein, regulates neurite outgrowth by modulating the Rho family of small GTPases.

scholarly journals Exposure to Copper Compromises the Maturational Competency of Porcine Oocytes by Impairing Mitochondrial Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Jingyue Chen ◽  
Zhaokang Cui ◽  
Yawei Qiu ◽  
Xingxing Zhang ◽  
Fang Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Reactive Oxygen ◽  
Oocyte Quality ◽  
Actin Dynamics ◽  
Oxygen Species ◽  
Cortical Granules ◽  
Porcine Oocyte ◽  
Mitochondrial Distribution ◽  
And Function

Copper (Cu) is an essential trace element for animals, and also an important nutritional component for the normal physiology and metabolism of animal reproductive systems. An excess or lack of Cu will directly or indirectly affect animal reproductive activities. However, the effect of Cu, in particular excessive Cu, on the reproductive performance of sows has not been studied. Here, we report that excessive Cu had negative effects on oocyte maturation and organelle functions. We showed that Cu exposure perturbed porcine oocyte meiotic maturation and impaired spindle/chromosome structure, resulting in a defective spindle assembly, as well as the abnormal distribution of actin dynamics and cortical granules. In addition, single-cell transcriptome analysis identified the target effectors of Cu actions in porcine oocytes, further demonstrating that Cu exposure affects the mitochondrial distribution and function, leading to the high levels of reactive oxygen species, DNA damage, and early apoptosis of porcine oocytes. These findings demonstrate that Cu exposure causes abnormalities in the mitochondrial distribution and function, resulting in the increased oxidative stress and levels of reactive oxygen species, DNA damage, and apoptosis, ultimately leading to a decreased porcine oocyte quality.

scholarly journals Plant iron nutrition in the long road from soil to seeds

2021 ◽  
Author(s):  
Irene Murgia ◽  
Francesca Marzorati ◽  
Gianpiero Vigani ◽  
Piero Morandini
Keyword(s):  
Reactive Oxygen Species ◽  
Control System ◽  
Life Cycle ◽  
Iron Nutrition ◽  
Oxygen Species ◽  
Cellular Processes ◽  
Early Seedling ◽  
Subcellular Compartmentalization ◽  
Fe Ions ◽  
Plant Iron Nutrition

Abstract Iron (Fe) is an essential plant micronutrient since photosynthesis, respiration, the scavenging of reactive oxygen species and many other cellular processes depend on adequate Fe levels. Nonetheless, non-complexed Fe ions can be dangerous for cells, as they can act as a pro-oxidant. Therefore, plants possess a complex homeostatic control system for safely taking up Fe from the soil, transporting it to the various cellular destinations and for its subcellular compartmentalization. At the end of the plant’s life cycle, maturing seeds are loaded with the required amount of Fe for germination and early seedling establishment. In this review, we discuss recent findings on how the microbiota in the rhizosphere influence and interact with the strategies adopted by plants to take up iron from the soil. We also focus on the process of seed loading with Fe and take into account the Fe metabolism in wild crops’ relatives. These aspects of plant Fe nutrition can represent promising avenues for a better comprehension of the long road of Fe from soil to seeds.

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