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 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 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 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 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 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.

scholarly journals GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge

2016 ◽  
Vol 27 (24) ◽  
pp. 3828-3840 ◽  
Author(s):  
Mengke Xing ◽  
Marshall C. Peterman ◽  
Robert L. Davis ◽  
Karen Oegema ◽  
Andrew K. Shiau ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Membrane Trafficking ◽  
Leading Edge ◽  
Invasion And Metastasis ◽  
Oncogenic Driver ◽  
Phosphatidylinositol 4 ◽  
Directional Cell Migration ◽  
Insight Into

The mechanism of directional cell migration remains an important problem, with relevance to cancer invasion and metastasis. GOLPH3 is a common oncogenic driver of human cancers, and is the first oncogene that functions at the Golgi in trafficking to the plasma membrane. Overexpression of GOLPH3 is reported to drive enhanced cell migration. Here we show that the phosphatidylinositol-4-phosphate/GOLPH3/myosin 18A/F-actin pathway that is critical for Golgi–to–plasma membrane trafficking is necessary and limiting for directional cell migration. By linking the Golgi to the actin cytoskeleton, GOLPH3 promotes reorientation of the Golgi toward the leading edge. GOLPH3 also promotes reorientation of lysosomes (but not other organelles) toward the leading edge. However, lysosome function is dispensable for migration and the GOLPH3 dependence of lysosome movement is indirect, via GOLPH3’s effect on the Golgi. By driving reorientation of the Golgi to the leading edge and driving forward trafficking, particularly to the leading edge, overexpression of GOLPH3 drives trafficking to the leading edge of the cell, which is functionally important for directional cell migration. Our identification of a novel pathway for Golgi reorientation controlled by GOLPH3 provides new insight into the mechanism of directional cell migration with important implications for understanding GOLPH3’s role in cancer.

scholarly journals Wnt5a Induces ROR1 to Complex with HS1, Which Undergoes Tyrosine Phosphorylation and Contributes to Planar-Cell-Polarity Migration in Chronic Lymphocytic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 301-301 ◽  
Author(s):  
Md Kamrul Hasan ◽  
Jian Yu ◽  
Liguang Chen ◽  
Bing Cui ◽  
Zhouxin Shen ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Tyrosine Phosphorylation ◽  
Cell Polarity ◽  
Research Funding ◽  
Actin Polymerization ◽  
Planar Cell Polarity ◽  
Leukemia Cell ◽  
Single Amino Acid ◽  
Mutant Form

Abstract ROR1 (Receptor tyrosine kinase-like orphan receptor 1) is an evolutionarily conserved, oncoembryonic antigen that is expressed on CLL cells, but not on normal postpartum tissues. In prior studies we found that ROR1 was a receptor for Wnt5a, which could activate RhoGTPases and enhance chemokine-directed leukemia-cell migration. Moreover, Wnt5a-enhanced migration could be inhibited by cirmtuzumab, a first-in-class humanized mAb specific for a functional epitope of the ROR1 extracellular domain; this mAb is undergoing phase I clinical testing in patients with CLL. However, it is not known whether ROR1 contributes to cell migration only through its recruitment/activation of guanine exchange factors (GEFs) or whether it also can complex with proteins that directly interact with the actin cytoskeleton. We performed mass spectrometry-based proteomics to interrogate immune-precipitates of Wnt5a-activated ROR1 from CLL cells and identified HS1 (or HCLS1, hematopoietic cell-specific Lyn substrate 1), a conserved cytoplasmic protein that can interact with the actin cytoskeleton. Moreover, tyrosine phosphorylation of HS1 has been found in prior studies to be associated with enhanced leukemia-cell migration and adverse prognosis in CLL, although the stimuli/mechanism(s) contributing to HS1 activation were unknown. We validated that Wnt5a induced the association of ROR1 with HS1 in primary CLL cells via co-immunoprecipitation studies and immunoblot analyses. Moreover, we found that Wnt5a could induce tyrosine phosphorylation of HS1 in CLL cells previously deprived of Wnt5a. On the other hand, treatment of CLL cells with the anti-ROR1 mAb cirmtuzumab inhibited the capacity of Wnt5a to induce the association of ROR1 with HS1 or tyrosine phosphorylation of HS1. We speculated that the Src-homology 3 (SH3) domain of HS1 allowed it to dock onto the cytoplasmic proline-rich domain (PRD) of ROR1. Consistent with this notion we found that a mutant-form of ROR1 lacking the PRD was unable to complex with HS1 or facilitate F-actin polymerization in response to Wnt5a. Accordingly, we used site-directed mutagenesis to introduce single amino acid substitutions of proline (P) to alanine (A) in the P-X-X-P- motifs of the ROR1 PRD at positions 784, 808, 826, 841, or 850. Each mutant form of ROR1, except for P841A-ROR1, could complex with HS1, permit tyrosine phosphorylation of HS1, and allow for enhanced leukemia-cell motility. Collectively, these data indicate that Wnt5a can induce HS1 to dock at P841 in the PRD of ROR1 and undergo tyrosine phosphorylation, thereby enhancing F-actin polymerization and planar-cell-polarity leukemia-cell migration. Moreover, we found that cirmtuzumab can inhibit activation of HS1 and F-actin polymerization in response to Wnt5a, potentially accounting in part for its capacity to inhibit Wnt5a-enhanced leukemia-cell migration. Disclosures Kipps: Gilead: Consultancy, Honoraria, Speakers Bureau; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria.

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