scholarly journals Homer3 regulates the establishment of neutrophil polarity

2015 ◽  
Vol 26 (9) ◽  
pp. 1629-1639 ◽  
Author(s):  
Julie Wu ◽  
Anne Pipathsouk ◽  
A. Keizer-Gunnink ◽  
F. Fusetti ◽  
W. Alkema ◽  
...  
Keyword(s):  
Cell Migration ◽  
Rna Interference ◽  
Cell Polarity ◽  
Actin Polymerization ◽  
Actin Assembly ◽  
Rac Gtpase ◽  
Gpcr Activation ◽  
Phosphoinositide 3 Kinase ◽  
Directional Cell Migration ◽  
Kinetics Of

Most chemoattractants rely on activation of the heterotrimeric G-protein Gαi to regulate directional cell migration, but few links from Gαi to chemotactic effectors are known. Through affinity chromatography using primary neutrophil lysate, we identify Homer3 as a novel Gαi2-binding protein. RNA interference–mediated knockdown of Homer3 in neutrophil-like HL-60 cells impairs chemotaxis and the establishment of polarity of phosphatidylinositol 3,4,5-triphosphate (PIP3) and the actin cytoskeleton, as well as the persistence of the WAVE2 complex. Most previously characterized proteins that are required for cell polarity are needed for actin assembly or activation of core chemotactic effectors such as the Rac GTPase. In contrast, Homer3-knockdown cells show normal magnitude and kinetics of chemoattractant-induced activation of phosphoinositide 3-kinase and Rac effectors. Chemoattractant-stimulated Homer3-knockdown cells also exhibit a normal initial magnitude of actin polymerization but fail to polarize actin assembly and intracellular PIP3 and are defective in the initiation of cell polarity and motility. Our data suggest that Homer3 acts as a scaffold that spatially organizes actin assembly to support neutrophil polarity and motility downstream of GPCR activation.

scholarly journals Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration

2020 ◽  
Vol 117 (25) ◽  
pp. 14270-14279
Author(s):  
Zhiwen Zhu ◽  
Yongping Chai ◽  
Huifang Hu ◽  
Wei Li ◽  
Wen-Jun Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Leading Edge ◽  
Receptor Activity ◽  
Actin Assembly ◽  
Neuroblast Migration ◽  
Directional Cell Migration ◽  
Migrating Cells

Directional cell migration involves signaling cascades that stimulate actin assembly at the leading edge, and additional pathways must inhibit actin polymerization at the rear. During neuroblast migration inCaenorhabditis elegans, the transmembrane protein MIG-13/Lrp12 acts through the Arp2/3 nucleation-promoting factors WAVE and WASP to guide the anterior migration. Here we show that a tyrosine kinase, SRC-1, directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. In GFP knockin animals, SRC-1 and MIG-13 distribute along the entire plasma membrane of migrating cells. We reveal that a receptor-like tyrosine phosphatase, PTP-3, maintains the F-actin polarity during neuroblast migration. Recombinant PTP-3 dephosphorylates SRC-1–dependent MIG-13 phosphorylation in vitro. Importantly, the endogenous PTP-3 accumulates at the rear of the migrating neuroblast, and its extracellular domain is essential for directional cell migration. We provide evidence that the asymmetrically localized tyrosine phosphatase PTP-3 spatially restricts MIG-13/Lrp12 receptor activity in migrating cells.

scholarly journals Prickle1mutation causes planar cell polarity and directional cell migration defects associated with cardiac outflow tract anomalies and other structural birth defects

Biology Open ◽  
2016 ◽  
Vol 5 (3) ◽  
pp. 323-335 ◽  
Author(s):  
Brian C. Gibbs ◽  
Rama Rao Damerla ◽  
Eszter K. Vladar ◽  
Bishwanath Chatterjee ◽  
Yong Wan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Birth Defects ◽  
Planar Cell Polarity ◽  
Outflow Tract ◽  
Directional Cell Migration ◽  
Cardiac Outflow

scholarly journals Cdc42 and Phosphoinositide 3-Kinase Drive Rac-Mediated Actin Polymerization Downstream of c-Met in Distinct and Common Pathways

2007 ◽  
Vol 27 (19) ◽  
pp. 6615-6628 ◽  
Author(s):  
Tanja Bosse ◽  
Julia Ehinger ◽  
Aleksandra Czuchra ◽  
Stefanie Benesch ◽  
Anika Steffen ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Actin Polymerization ◽  
Pi3 Kinase ◽  
Actin Assembly ◽  
Actin Reorganization ◽  
Membrane Ruffling ◽  
Internalin B ◽  
Phosphoinositide 3 Kinase ◽  
Hepatocyte Growth ◽  
Wave Complex

ABSTRACT Activation of c-Met, the hepatocyte growth factor (HGF)/scatter factor receptor induces reorganization of the actin cytoskeleton, which drives epithelial cell scattering and motility and is exploited by pathogenic Listeria monocytogenes to invade nonepithelial cells. However, the precise contributions of distinct Rho-GTPases, the phosphatidylinositol 3-kinases, and actin assembly regulators to c-Met-mediated actin reorganization are still elusive. Here we report that HGF-induced membrane ruffling and Listeria invasion mediated by the bacterial c-Met ligand internalin B (InlB) were significantly impaired but not abrogated upon genetic removal of either Cdc42 or pharmacological inhibition of phosphoinositide 3-kinase (PI3-kinase). While loss of Cdc42 or PI3-kinase function correlated with reduced HGF- and InlB-triggered Rac activation, complete abolishment of actin reorganization and Rac activation required the simultaneous inactivation of both Cdc42 and PI3-kinase signaling. Moreover, Cdc42 activation was fully independent of PI3-kinase activity, whereas the latter partly depended on Cdc42. Finally, Cdc42 function did not require its interaction with the actin nucleation-promoting factor N-WASP. Instead, actin polymerization was driven by Arp2/3 complex activation through the WAVE complex downstream of Rac. Together, our data establish an intricate signaling network comprising as key molecules Cdc42 and PI3-kinase, which converge on Rac-mediated actin reorganization essential for Listeria invasion and membrane ruffling downstream of c-Met.

scholarly journals Connexin43 Modulates Cell Polarity and Directional Cell Migration by Regulating Microtubule Dynamics

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e26379 ◽  
Author(s):  
Richard Francis ◽  
Xin Xu ◽  
Hyunsoo Park ◽  
Chin-Jen Wei ◽  
Stephen Chang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Microtubule Dynamics ◽  
Directional Cell Migration

scholarly journals Distinct phospho-forms of cortactin differentially regulate actin polymerization and focal adhesions

2008 ◽  
Vol 295 (5) ◽  
pp. C1113-C1122 ◽  
Author(s):  
Anne E. Kruchten ◽  
Eugene W. Krueger ◽  
Yu Wang ◽  
Mark A. McNiven
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Actin Polymerization ◽  
Control Cell ◽  
Focal Adhesions ◽  
Serine Phosphorylation ◽  
Actin Binding ◽  
Actin Assembly

Cortactin is an actin-binding protein that is overexpressed in many cancers and is a substrate for both tyrosine and serine/threonine kinases. Tyrosine phosphorylation of cortactin has been observed to increase cell motility and invasion in vivo, although it has been reported to have both positive and negative effects on actin polymerization in vitro. In contrast, serine phosphorylation of cortactin has been shown to stimulate actin assembly in vitro. Currently, the effects of cortactin serine phosphorylation on cell migration are unclear, and furthermore, how the distinct phospho-forms of cortactin may differentially contribute to cell migration has not been directly compared. Therefore, we tested the effects of different tyrosine and serine phospho-mutants of cortactin on lamellipodial protrusion, actin assembly within cells, and focal adhesion dynamics. Interestingly, while expression of either tyrosine or serine phospho-mimetic cortactin mutants resulted in increased lamellipodial protrusion and cell migration, these effects appeared to be via distinct processes. Cortactin mutants mimicking serine phosphorylation appeared to predominantly affect actin polymerization, whereas mutation of cortactin tyrosine residues resulted in alterations in focal adhesion turnover. Thus these findings provide novel insights into how distinct phospho-forms of cortactin may differentially contribute to actin and focal adhesion dynamics to control cell migration.

scholarly journals Wdpcp, a PCP Protein Required for Ciliogenesis, Regulates Directional Cell Migration and Cell Polarity by Direct Modulation of the Actin Cytoskeleton

PLoS Biology ◽  
2013 ◽  
Vol 11 (11) ◽  
pp. e1001720 ◽  
Author(s):  
Cheng Cui ◽  
Bishwanath Chatterjee ◽  
Thomas P. Lozito ◽  
Zhen Zhang ◽  
Richard J. Francis ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Cell Polarity ◽  
Direct Modulation ◽  
Directional Cell Migration

scholarly journals A small part of myosin IIB takes on a big role in cell polarity

2015 ◽  
Vol 209 (1) ◽  
pp. 11-12 ◽  
Author(s):  
Aidan M. Fenix ◽  
Dylan T. Burnette
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Nonmuscle Myosin ◽  
New Paradigm ◽  
Cell Biol ◽  
Directional Cell Migration

A migrating cell must establish front-to-back polarity in order to move. In this issue, Juanes-Garcia et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201407059) report that a short serine-rich motif in nonmuscle myosin IIB is required to establish the cell’s rear. This motif represents a new paradigm for what determines directional cell migration.

scholarly journals Mechanochemical feedback underlies coexistence of qualitatively distinct cell polarity patterns within diverse cell populations

2017 ◽  
Vol 114 (28) ◽  
pp. E5750-E5759 ◽  
Author(s):  
JinSeok Park ◽  
William R. Holmes ◽  
Sung Hoon Lee ◽  
Hong-Nam Kim ◽  
Deok-Ho Kim ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cell Types ◽  
Small Gtpases ◽  
Cell Polarization ◽  
Environmental Perturbations ◽  
Oscillatory Dynamic ◽  
Distinct Cell ◽  
Spatially Distributed ◽  
Directional Cell Migration

Cell polarization and directional cell migration can display random, persistent, and oscillatory dynamic patterns. However, it is not clear whether these polarity patterns can be explained by the same underlying regulatory mechanism. Here, we show that random, persistent, and oscillatory migration accompanied by polarization can simultaneously occur in populations of melanoma cells derived from tumors with different degrees of aggressiveness. We demonstrate that all of these patterns and the probabilities of their occurrence are quantitatively accounted for by a simple mechanism involving a spatially distributed, mechanochemical feedback coupling the dynamically changing extracellular matrix (ECM)–cell contacts to the activation of signaling downstream of the Rho-family small GTPases. This mechanism is supported by a predictive mathematical model and extensive experimental validation, and can explain previously reported results for diverse cell types. In melanoma, this mechanism also accounts for the effects of genetic and environmental perturbations, including mutations linked to invasive cell spread. The resulting mechanistic understanding of cell polarity quantitatively captures the relationship between population variability and phenotypic plasticity, with the potential to account for a wide variety of cell migration states in diverse pathological and physiological conditions.

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