scholarly journals ERM Proteins at the Crossroad of Leukocyte Polarization, Migration and Intercellular Adhesion

2020 ◽  
Vol 21 (4) ◽  
pp. 1502 ◽  
Author(s):  
Almudena García-Ortiz ◽  
Juan Manuel Serrador
Keyword(s):  
Rho Gtpases ◽  
Transmembrane Proteins ◽  
Cellular Structures ◽  
Ferm Domain ◽  
Erm Proteins ◽  
Immune Synapse ◽  
Small Rho Gtpases ◽  
And Migration ◽  
Wide Assortment ◽  
Effector Immune Response

Ezrin, radixin and moesin proteins (ERMs) are plasma membrane (PM) organizers that link the actin cytoskeleton to the cytoplasmic tail of transmembrane proteins, many of which are adhesion receptors, in order to regulate the formation of F-actin-based structures (e.g., microspikes and microvilli). ERMs also effect transmission of signals from the PM into the cell, an action mainly exerted through the compartmentalized activation of the small Rho GTPases Rho, Rac and Cdc42. Ezrin and moesin are the ERMs more highly expressed in leukocytes, and although they do not always share functions, both are mainly regulated through phosphatidylinositol 4,5-bisphosphate (PIP2) binding to the N-terminal band 4.1 protein-ERM (FERM) domain and phosphorylation of a conserved Thr in the C-terminal ERM association domain (C-ERMAD), exerting their functions through a wide assortment of mechanisms. In this review we will discuss some of these mechanisms, focusing on how they regulate polarization and migration in leukocytes, and formation of actin-based cellular structures like the phagocytic cup-endosome and the immune synapse in macrophages/neutrophils and lymphocytes, respectively, which represent essential aspects of the effector immune response.

scholarly journals Cortical Interneuron Development: a role for small Rho GTPases

2021 ◽  
Author(s):  
Zouzana Kounoupa ◽  
Domna Karagogeos
Keyword(s):  
Cell Cycle ◽  
Rho Gtpases ◽  
Double Mutant ◽  
Epileptic Seizures ◽  
Transgenic Animals ◽  
Postnatal Period ◽  
Cell Therapies ◽  
Cortical Interneurons ◽  
Small Rho Gtpases ◽  
And Migration

GABAergic interneurons control cortical excitation/inhibition balance and are implicated in severe neurodevelopmental disorders. In contrast to the multiplicity of signals underlying the generation and migration of cortical interneurons, the intracellular proteins mediating the response to these cues are mostly unknown. We have demonstrated the unique and diverse roles of the Rho GTPases Rac1 and 3 in cell cycle and morphology in transgenic animals where Rac1 and Rac1/3 were ablated specifically in cortical interneurons. In the Rac1 mutant, progenitors delay their cell cycle exit probably due to a prolonged G1 phase resulting in a cortex with 50% reductions in interneurons and an imbalance of excitation/inhibition in cortical circuits. This disruption in GABAergic inhibition alters glutamatergic function in the adult cortex that could be reversed by enhancement of GABAergic function during an early postnatal period. Furthermore, this disruption disturbs the neuronal synchronization in the adult cortex. In the double mutant, additional severe cytoskeletal defects result in an 80% interneuron decrease. Both lines die from epileptic seizures postnatally. We have made progress towards characterizing the cell cycle defect in Rac1 mutant interneuron progenitors, determining the morphological and synaptic characteristics of single and double mutant interneurons and identifying some of the molecular players by which Racs exert their actions by proteomic analysis. In our present work, we review these studies and discuss open questions and future perspectives. We expect that our data will contribute to the understanding of the function of cortical interneurons, especially since preclinical models of interneuron-based cell therapies are being established.

scholarly journals Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

Oncogene ◽  
2020 ◽  
Vol 39 (18) ◽  
pp. 3666-3679 ◽  
Author(s):  
Mario De Piano ◽  
Valeria Manuelli ◽  
Giorgia Zadra ◽  
Jonathan Otte ◽  
Per-Henrik D. Edqvist ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Adhesion ◽  
Cancer Cell ◽  
Rho Gtpases ◽  
Prostate Cancer Cell ◽  
Cancer Cell Adhesion ◽  
Cell Adhesion And Migration ◽  
And Migration

Distinct signals via Rho GTPases and Src drive shape changes by thrombin and sphingosine-1-phosphate in endothelial cells

2002 ◽  
Vol 115 (12) ◽  
pp. 2475-2484 ◽  
Author(s):  
Valérie Vouret-Craviari ◽  
Christine Bourcier ◽  
Etienne Boulter ◽  
Ellen Van Obberghen-Schilling
Keyword(s):  
Endothelial Cells ◽  
Rho Gtpases ◽  
Actin Polymerization ◽  
Morphological Changes ◽  
Umbilical Vein ◽  
Cell Spreading ◽  
Actin Binding ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells

Soluble mediators such as thrombin and sphingosine-1-phosphate regulate morphological changes in endothelial cells that affect vascular permeability and new blood vessel formation. Although these ligands activate a similar set of heterotrimeric G proteins, thrombin causes cell contraction and rounding whereas sphingosine-1-phosphate induces cell spreading and migration. A functional requirement for Rho family GTPases in the cytoskeletal responses to both ligands has been established, yet the dynamics of their regulation and additional signaling mechanisms that lead to such opposite effects remain poorly understood. Using a pull-down assay to monitor the activity of Rho GTPases in human umbilical vein endothelial cells, we find significant temporal and quantitative differences in RhoA and Rac1 activation. High levels of active RhoA rapidly accumulate in cells in response to thrombin whereas Rac1 is inhibited. In contrast, sphingosine-1-phosphate addition leads to comparatively weak and delayed activation of RhoA and it activates Rac1. In addition, we show here that sphingosine-1-phosphate treatment activates a Src family kinase and triggers recruitment of the F-actin-binding protein cortactin to sites of actin polymerization at the rim of membrane ruffles. Both Src and Rac pathways are essential for lamellipodia targeting of cortactin. Further, Src plays a determinant role in sphingosine-1-phosphate-induced cell spreading and migration. Taken together these data demonstrate that the thrombin-induced contractile and immobile phenotype in endothelial cells reflects both robust RhoA activation and Rac inhibition, whereas Src- and Rac-dependent events couple sphingosine-1-phosphate receptors to the actin polymerizing machinery that drives the extension of lamellipodia and cell migration.

Small Rho GTPases in the control of cell shape and mobility

2013 ◽  
Vol 71 (9) ◽  
pp. 1703-1721 ◽  
Author(s):  
Arun Murali ◽  
Krishnaraj Rajalingam
Keyword(s):  
Rho Gtpases ◽  
Cell Shape ◽  
Small Rho Gtpases

scholarly journals CB-15 * NKCC1 REGULATES MIGRATION CAPACITY OF GLIOBLASTOMA TUMOR INITIATING CELLS BY MODULATING ACTIN CYTOSKELETON THROUGH SMALL RHO GTPASES

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v43-v44 ◽  
Author(s):  
P. Schiapparelli ◽  
R. Magana-Maldonado ◽  
S. Hamilla ◽  
L. Sibener ◽  
J. C. Martinez-Gutierrez ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Tumor Initiating Cells ◽  
Small Rho Gtpases ◽  
Migration Capacity

scholarly journals Small Rho GTPases and Cholesterol Biosynthetic Pathway Intermediates in African Swine Fever Virus Infection

2011 ◽  
Vol 86 (3) ◽  
pp. 1758-1767 ◽  
Author(s):  
J. I. Quetglas ◽  
B. Hernaez ◽  
I. Galindo ◽  
R. Munoz-Moreno ◽  
M. A. Cuesta-Geijo ◽  
...  
Keyword(s):  
Virus Infection ◽  
Rho Gtpases ◽  
Biosynthetic Pathway ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Small Rho Gtpases ◽  
Cholesterol Biosynthetic Pathway
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