Cell Polarity and Migration: Emerging Role for the Endosomal Sorting Machinery

Physiology ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 171-180 ◽  
Author(s):  
Viola Hélène Lobert ◽  
Harald Stenmark
Keyword(s):  
Cell Migration ◽  
Cell Division ◽  
Cell Polarity ◽  
Tumor Suppressors ◽  
Potential Role ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Viral Budding ◽  
And Migration

The endosomal sorting complex required for transport (ESCRT) machinery has been implicated in the regulation of endosomal sorting, cell division, viral budding, autophagy, and cell signaling. Here, we review recent evidence that implicates ESCRTs in cell polarity and cell migration, and discuss the potential role of ESCRTs as tumor suppressors.

scholarly journals P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

2016 ◽  
Vol 212 (2) ◽  
pp. 199-217 ◽  
Author(s):  
Cédric Plutoni ◽  
Elsa Bazellieres ◽  
Maïlys Le Borgne-Rochet ◽  
Franck Comunale ◽  
Agusti Brugues ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cell Biology ◽  
Cell Polarization ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Tumor Aggressiveness ◽  
And Migration ◽  
Cell Cell

Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

scholarly journals ESCRT-dependent targeting of plasma membrane localized KCa3.1 to the lysosomes

2010 ◽  
Vol 299 (5) ◽  
pp. C1015-C1027 ◽  
Author(s):  
Corina M. Balut ◽  
Yajuan Gao ◽  
Sandra A. Murray ◽  
Patrick H. Thibodeau ◽  
Daniel C. Devor
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Close Association ◽  
Significant Inhibition ◽  
Dominant Negative ◽  
Human Embryonic Kidney Cells ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Interfering Rna

The number of intermediate-conductance, Ca2+-activated K+ channels (KCa3.1) present at the plasma membrane is deterministic in any physiological response. However, the mechanisms by which KCa3.1 channels are removed from the plasma membrane and targeted for degradation are poorly understood. Recently, we demonstrated that KCa3.1 is rapidly internalized from the plasma membrane, having a short half-life in both human embryonic kidney cells (HEK293) and human microvascular endothelial cells (HMEC-1). In this study, we investigate the molecular mechanisms controlling the degradation of KCa3.1 heterologously expressed in HEK and HMEC-1 cells. Using immunofluorescence and electron microscopy, as well as quantitative biochemical analysis, we demonstrate that membrane KCa3.1 is targeted to the lysosomes for degradation. Furthermore, we demonstrate that either overexpressing a dominant negative Rab7 or short interfering RNA-mediated knockdown of Rab7 results in a significant inhibition of channel degradation rate. Coimmunoprecipitation confirmed a close association between Rab7 and KCa3.1. On the basis of these findings, we assessed the role of the ESCRT machinery in the degradation of heterologously expressed KCa3.1, including TSG101 [endosomal sorting complex required for transport (ESCRT)-I] and CHMP4 (ESCRT-III) as well as VPS4, a protein involved in the disassembly of the ESCRT machinery. We demonstrate that TSG101 is closely associated with KCa3.1 via coimmunoprecipitation and that a dominant negative TSG101 inhibits KCa3.1 degradation. In addition, both dominant negative CHMP4 and VPS4 significantly decrease the rate of membrane KCa3.1 degradation, compared with wild-type controls. These results are the first to demonstrate that plasma membrane-associated KCa3.1 is targeted for lysosomal degradation via a Rab7 and ESCRT-dependent pathway.

scholarly journals WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment

2018 ◽  
Vol 115 (34) ◽  
pp. 8581-8586 ◽  
Author(s):  
Pengbo Wang ◽  
Marcel Dreger ◽  
Elena Madrazo ◽  
Craig J. Williams ◽  
Rafael Samaniego ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Underlying Mechanism ◽  
H3k4 Methylation ◽  
Nuclear Mechanics ◽  
3D Environment ◽  
3D Environments ◽  
And Migration

Cell migration through extracellular matrices requires nuclear deformation, which depends on nuclear stiffness. In turn, chromatin structure contributes to nuclear stiffness, but the mechanosensing pathways regulating chromatin during cell migration remain unclear. Here, we demonstrate that WD repeat domain 5 (WDR5), an essential component of H3K4 methyltransferase complexes, regulates cell polarity, nuclear deformability, and migration of lymphocytes in vitro and in vivo, independent of transcriptional activity, suggesting nongenomic functions for WDR5. Similarly, depletion of RbBP5 (another H3K4 methyltransferase subunit) promotes similar defects. We reveal that a 3D environment increases the H3K4 methylation dependent on WDR5 and results in a globally less compacted chromatin conformation. Further, using atomic force microscopy, nuclear particle tracking, and nuclear swelling experiments, we detect changes in nuclear mechanics that accompany the epigenetic changes induced in 3D conditions. Indeed, nuclei from cells in 3D environments were softer, and thereby more deformable, compared with cells in suspension or cultured in 2D conditions, again dependent on WDR5. Dissecting the underlying mechanism, we determined that actomyosin contractility, through the phosphorylation of myosin by MLCK (myosin light chain kinase), controls the interaction of WDR5 with other components of the methyltransferase complex, which in turn up-regulates H3K4 methylation activation in 3D conditions. Taken together, our findings reveal a nongenomic function for WDR5 in regulating H3K4 methylation induced by 3D environments, physical properties of the nucleus, cell polarity, and cell migratory capacity.

scholarly journals Fine Tuning Cell Migration by a Disintegrin and Metalloproteinases

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
D. Dreymueller ◽  
K. Theodorou ◽  
M. Donners ◽  
A. Ludwig
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Immune Cell ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
Tissue Cell ◽  
Cancer Cell Migration ◽  
Physiological Processes ◽  
Cell Tissue ◽  
And Migration

Cell migration is an instrumental process involved in organ development, tissue homeostasis, and various physiological processes and also in numerous pathologies. Both basic cell migration and migration towards chemotactic stimulus consist of changes in cell polarity and cytoskeletal rearrangement, cell detachment from, invasion through, and reattachment to their neighboring cells, and numerous interactions with the extracellular matrix. The different steps of immune cell, tissue cell, or cancer cell migration are tightly coordinated in time and place by growth factors, cytokines/chemokines, adhesion molecules, and receptors for these ligands. This review describes how a disintegrin and metalloproteinases interfere with several steps of cell migration, either by proteolytic cleavage of such molecules or by functions independent of proteolytic activity.

The Potential Role of SnRK1 Protein Kinases in the Regulation of Cell Division in Arabidopsis thaliana

2019 ◽  
Vol 53 (3) ◽  
pp. 185-191 ◽  
Author(s):  
O. E. Krasnoperova ◽  
D. D. Buy ◽  
I. I. Goriunova ◽  
S. V. Isayenkov ◽  
P. A. Karpov ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Cell Division ◽  
Protein Kinases ◽  
Potential Role

The integrin alphavbeta6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectin

1998 ◽  
Vol 111 (15) ◽  
pp. 2189-2195 ◽  
Author(s):  
X. Huang ◽  
J. Wu ◽  
S. Spong ◽  
D. Sheppard
Keyword(s):  
Cell Migration ◽  
Tissue Injury ◽  
Critical Role ◽  
Cell Behavior ◽  
Wild Type ◽  
Migration Assays ◽  
And Migration ◽  
Hepatocyte Growth

The integrin alphavbeta6 is expressed on a variety of epithelial cells during dynamic processes including organogenesis, tissue injury and malignant transformation. However, because of the lack of tools to specifically inhibit the function of this integrin, little is known about its effects on cell behavior. To directly examine the role of this integrin in cell migration, we used keratinocytes derived from wild-type mice or mice expressing a null mutation in the beta6 subunit (beta6-/-) to perform migration assays in vitro. Migration on the known alphavbeta6 ligand, fibronectin was reduced in keratinocytes from beta6-/- mice. Interestingly, keratinocytes from beta6-/- mice also demonstrated markedly reduced migration on vitronectin, a protein not previously known to be a ligand for alphavbeta6. An anti-alphavbeta6 monoclonal antibody 10D5, generated by immunization of beta6-/- mice with murine keratinocytes, inhibited adhesion and migration of wild-type keratinocyte on both vitronectin and fibronectin to levels similar to those seen with keratinocytes from beta6-/- mice. alphavbeta6-mediated migration on both ligands was dramatically augmented by treatment with phorbol myrisate acetate (PMA) or with hepatocyte growth factor, and augmentation of migration by either stimulus could be abolished by the PKC inhibitor GF109203X, suggesting a critical role for PKC in enhancement of alphavbeta6-mediated cell migration.

547 THE ROLE OF HEAT SHOCK PROTEIN 90 IN HYPOXIA INDUCED ANGIOGENESIS AND EPITHELIAL-MESENCHYMAL TRANSITION OF ESOPHAGEAL SQUAMOUS CELL CANCER

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Ching Tzao ◽  
Chin-Kun Wang
Keyword(s):  
Cell Migration ◽  
Heat Shock ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Esophageal Squamous Cell Cancer ◽  
Mesenchymal Transition ◽  
And Migration

Abstract   Hypoxia is known as an important trigger for the development of metastases in human cancers. Heat shock proteins (Hsps) are up-regulated by cellular stressors including hypoxia. To date, the functional role of Hsps within the hypoxic tumor microenvironment for esophageal squamous cell cancer (ESCC) remains poorly defined. Methods CoCl₂ was used to induce hypoxia in cultured ESCC cells which was confirmed by 2′,7′ –dichlorofluorescin diacetate (DCFDA) assay. 7-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a selective Hsp90 inhibitor, was used to treat 2 ESCC cell lines, KYSE-170 and -510 cells pretreated with or without CoCl₂₂₂₂₂ in different concentrations, followed by cytotoxicity (MTT) and migration assays. In parallel, expression of Hsp90, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), and markers related to epithelial-mesenchymal transition (EMT) such as snail/E-cadherin, by immunoblot or ELISA while analyzing cell proliferation and migration of treated ESCC cells. Results CoCl₂ induced hypoxia was supported by induction of reactive oxygen species (ROS). CoCl₂ (200 μM) significantly suppressed cell viability and proliferation with a concomitant up-regulation of VEGF and HIF-1α in a dose-dependent fashion. In contrast, cell migration was significantly increased in response to CoCl₂ while down-regulating E-cadherin with a concomitant increase in Snail expression. 17-DMAG decreased expression of VEGF and HIF-1α while inhibiting cell migration and invasion. Conclusion Our data demonstrate that CoCl2 induced hypoxia promotes EMT and angiogensis, which are inhibited by 17-DMAG. These results suggest that hypoxia induced EMT and angiogensis is Hsp90 dependent in ESCC.

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