scholarly journals Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis

2011 ◽  
Vol 68 (23) ◽  
pp. 3933-3947 ◽  
Author(s):  
Elma Aflaki ◽  
Nariman A. B. Balenga ◽  
Petra Luschnig-Schratl ◽  
Heimo Wolinski ◽  
Silvia Povoden ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Cell Polarization ◽  
Gtpase Activation ◽  
And Migration

scholarly journals Erratum to: Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis

2013 ◽  
Vol 70 (14) ◽  
pp. 2621-2621 ◽  
Author(s):  
Elma Aflaki ◽  
Nariman A. B. Balenga ◽  
Petra Luschnig-Schratl ◽  
Heimo Wolinski ◽  
Silvia Povoden ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Cell Polarization ◽  
Gtpase Activation ◽  
And Migration

scholarly journals Pin1 Regulates IL-5 Induced Eosinophil Polarization and Migration

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 211
Author(s):  
Zhong-Jian Shen ◽  
Jie Hu ◽  
Melissa A. O’Neal ◽  
James S. Malter
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Rho Gtpase ◽  
Shape Change ◽  
Cell Polarization ◽  
Gtpase Activity ◽  
Prolyl Isomerase ◽  
Directional Migration ◽  
Migration Polarization ◽  
And Migration

Eosinophils become polarized in response to cytokines such IL-5 or eotaxin prior to directional migration. Polarization is preceded by F-actin assembly, but the mechanisms that regulate these events and how the shape change influences cell migration from the peripheral blood into the lung remain unclear. In this study, we show that the prolyl isomerase, Pin1, is required for IL-5-induced Eos polarization and migration. Co-immunoprecipitation and immunofluorescence analysis revealed that Pin1 directly interacts with members of Rho GTPase family. Mouse eosinophils lacking Pin1 or human cells treated with Pin1 inhibitors showed significantly reduced IL-5-induced GTPase activity and cofilin phosphorylation, resulting in reduced F-actin polymerization, cell polarization, and directional migration to chemokines. Our result suggests that Pin1 regulates cytoskeletal re-organization, eosinophil morphology, and cell migration through the modulation of Rho GTPase activity. Targeting Pin1 along with GTPases could provide a new approach to reduce pulmonary Eos accumulation during asthmatic exacerbations.

scholarly journals Effects of Structure of Rho GTPase-activating Protein DLC-1 on Cell Morphology and Migration

2008 ◽  
Vol 283 (47) ◽  
pp. 32762-32770 ◽  
Author(s):  
Tai Young Kim ◽  
Kevin D. Healy ◽  
Channing J. Der ◽  
Noah Sciaky ◽  
Yung-Jue Bang ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Rho Gtpase ◽  
Gtpase Activating Protein ◽  
And Migration

scholarly journals Chronic lymphocytic leukemia cells induce defective LFA-1–directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide

Blood ◽  
2013 ◽  
Vol 121 (14) ◽  
pp. 2704-2714 ◽  
Author(s):  
Alan G. Ramsay ◽  
Rachel Evans ◽  
Shahryar Kiaii ◽  
Lena Svensson ◽  
Nancy Hogg ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Motility ◽  
Rho Gtpase ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Key Points ◽  
Gtpase Activation ◽  
Activation Signaling

Key Points CLL cells induce defects in T-cell LFA-1–mediated migration by altering Rho GTPase activation signaling, downregulating RhoA and Rac1, and upregulating Cdc42. Lenalidomide repairs these T-cell defects by restoring normal Rho GTPase activation signaling.

scholarly journals Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1990
Author(s):  
Inmaculada Navarro-Lérida ◽  
Miguel Sánchez-Álvarez ◽  
Miguel Ángel del Pozo
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Protein Complexes ◽  
Specific Protein ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Post Translational Modification ◽  
Functional Regulation ◽  
Subcellular Compartmentalization ◽  
Cellular Compartments

Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

scholarly journals Histone deacetylase 6-mediated deacetylation of α-tubulin coordinates cytoskeletal and signaling events during platelet activation

2013 ◽  
Vol 305 (12) ◽  
pp. C1230-C1239 ◽  
Author(s):  
Joseph E. Aslan ◽  
Kevin G. Phillips ◽  
Laura D. Healy ◽  
Asako Itakura ◽  
Jiaqing Pang ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Rho Gtpase ◽  
Specific Inhibitor ◽  
Covalent Modification ◽  
Histone Deacetylase 6 ◽  
Signaling Systems ◽  
Glycoprotein Vi ◽  
Marginal Band ◽  
Signaling Events ◽  
Gtpase Activation

The tubulin cytoskeleton plays a key role in maintaining the characteristic quiescent discoid shape of resting platelets. Upon activation, platelets undergo a dramatic change in shape; however, little is known of how the microtubule system contributes to regulating platelet shape and function. Here we investigated the role of the covalent modification of α-tubulin by acetylation in the regulation of platelet physiology during activation. Superresolution microscopy analysis of the platelet tubulin cytoskeleton showed that the marginal band together with an interconnected web of finer tubulin structures collapsed upon platelet activation with the glycoprotein VI (GPVI)-agonist collagen-related peptide (CRP). Western blot analysis revealed that α-tubulin was acetylated in resting platelets and deacetylated during platelet activation. Tubacin, a specific inhibitor of the tubulin deacetylase HDAC6, prevented tubulin deacetylation upon platelet activation with CRP. Inhibition of HDAC6 upregulated tubulin acetylation and disrupted the organization of the platelet microtubule marginal band without significantly affecting platelet volume changes in response to CRP stimulation. HDAC6 inhibitors also inhibited platelet aggregation in response to CRP and blocked platelet signaling events upstream of platelet Rho GTPase activation. Together, these findings support a role for acetylation signaling in controlling the resting structure of the platelet tubulin marginal band as well as in the coordination of signaling systems that drive platelet cytoskeletal changes and aggregation.

scholarly journals The inositol 5-phosphatase SHIP2 is an effector of RhoA and is involved in cell polarity and migration

2012 ◽  
Vol 23 (13) ◽  
pp. 2593-2604 ◽  
Author(s):  
Katsuhiro Kato ◽  
Tsubasa Yazawa ◽  
Kentaro Taki ◽  
Kazutaka Mori ◽  
Shujie Wang ◽  
...  
Keyword(s):  
Small Gtpases ◽  
Cell Polarization ◽  
Dependent Manner ◽  
Wild Type ◽  
Functional Interaction ◽  
Src Homology 2 ◽  
Motile Cells ◽  
Lipid Turnover ◽  
Src Homology ◽  
And Migration

Cell migration is essential for various physiological and pathological processes. Polarization in motile cells requires the coordination of several key signaling molecules, including RhoA small GTPases and phosphoinositides. Although RhoA participates in a front–rear polarization in migrating cells, little is known about the functional interaction between RhoA and lipid turnover. We find here that src-homology 2–containing inositol-5-phosphatase 2 (SHIP2) interacts with RhoA in a GTP-dependent manner. The association between SHIP2 and RhoA is observed in spreading and migrating U251 glioma cells. The depletion of SHIP2 attenuates cell polarization and migration, which is rescued by wild-type SHIP2 but not by a mutant defective in RhoA binding. In addition, the depletion of SHIP2 impairs the proper localization of phosphatidylinositol 3,4,5-trisphosphate, which is not restored by a mutant defective in RhoA binding. These results suggest that RhoA associates with SHIP2 to regulate cell polarization and migration.

scholarly journals CaM kinase IIδ2-dependent regulation of vascular smooth muscle cell polarization and migration

2008 ◽  
Vol 294 (6) ◽  
pp. C1465-C1475 ◽  
Author(s):  
Melissa Z. Mercure ◽  
Roman Ginnan ◽  
Harold A. Singer
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Cell Monolayer ◽  
Leading Edge ◽  
Cell Polarization ◽  
Loss Of Function ◽  
Downstream Signaling ◽  
Transient Activation ◽  
And Migration

Previous studies indicate involvement of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) in vascular smooth muscle (VSM) cell migration. In the present study, molecular loss-of-function studies were used specifically to assess the role of the predominant CaMKIIδ2 isoform on VSM cell migration using a scratch wound healing assay. Targeted CaMKIIδ2 knockdown using siRNA or inhibition of activity by overexpressing a kinase-negative mutant resulted in attenuation of VSM cell migration. Temporal and spatial assessments of kinase autophosphorylation indicated rapid and transient activation in response to wounding, in addition to a sustained activation in the leading edge of migrating and spreading cells. Furthermore, siRNA-mediated suppression of CaMKIIδ2 resulted in the inhibition of wound-induced Rac activation and Golgi reorganization, and disruption of leading edge morphology, indicating an important function for CaMKIIδ2 in regulating VSM cell polarization. Numerous previous reports link activation of CaMKII to ERK1/2 signaling in VSM. Wound-induced ERK1/2 activation was also found to be dependent on CaMKII; however, ERK activity did not account for effects of CaMKII in regulating Golgi polarization, indicating alternative mechanisms by which CaMKII affects the complex events involved in cell migration. Wounding a VSM cell monolayer results in CaMKIIδ2 activation, which positively regulates VSM cell polarization and downstream signaling, including Rac and ERK1/2 activation, leading to cell migration.

scholarly journals Localized Rho GTPase Activation Regulates RNA Dynamics and Compartmentalization in Tumor Cell Protrusions

2008 ◽  
Vol 283 (50) ◽  
pp. 34785-34795 ◽  
Author(s):  
Heather C. Stuart ◽  
Zongjian Jia ◽  
Anat Messenberg ◽  
Bharat Joshi ◽  
T. Michael Underhill ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Rho Gtpase ◽  
Rna Dynamics ◽  
Gtpase Activation
Sign in / Sign up

Export Citation Format

Share Document