scholarly journals EWI-2 regulates α3β1 integrin–dependent cell functions on laminin-5

2003 ◽  
Vol 163 (5) ◽  
pp. 1167-1177 ◽  
Author(s):  
Christopher S. Stipp ◽  
Tatiana V. Kolesnikova ◽  
Martin E. Hemler
Keyword(s):  
Cell Migration ◽  
Complex Formation ◽  
Cell Surface ◽  
Laminin 5 ◽  
Cell Functions ◽  
Α3β1 Integrin ◽  
Surface Localization ◽  
Dependent Cell ◽  
A Cell ◽  
Integrin Ligand

EWI-2, a cell surface immunoglobulin SF protein of unknown function, associates with tetraspanins CD9 and CD81 with high stoichiometry. Overexpression of EWI-2 in A431 epidermoid carcinoma cells did not alter cell adhesion or spreading on laminin-5, and had no effect on reaggregation of cells plated on collagen I (α2β1 integrin ligand). However, on laminin-5 (α3β1 integrin ligand), A431 cell reaggregation and motility functions were markedly impaired. Immunodepletion and reexpression experiments revealed that tetraspanins CD9 and CD81 physically link EWI-2 to α3β1 integrin, but not to other integrins. CD81 also controlled EWI-2 maturation and cell surface localization. EWI-2 overexpression not only suppressed cell migration, but also redirected CD81 to cell filopodia and enhanced α3β1–CD81 complex formation. In contrast, an EWI-2 chimeric mutant failed to suppress cell migration, redirect CD81 to filopodia, or enhance α3β1–CD81 complex formation. These results show how laterally associated EWI-2 might regulate α3β1 function in disease and development, and demonstrate how tetraspanin proteins can assemble multiple nontetraspanin proteins into functional complexes.

The interaction of enolase-1 with caveolae-associated proteins regulates its subcellular localization

2014 ◽  
Vol 460 (2) ◽  
pp. 295-307 ◽  
Author(s):  
Dariusz Zakrzewicz ◽  
Miroslava Didiasova ◽  
Anna Zakrzewicz ◽  
Andreas C. Hocke ◽  
Florian Uhle ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Subcellular Localization ◽  
Migration And Invasion ◽  
Caveolin 1 ◽  
Annexin 2 ◽  
Associated Proteins ◽  
Surface Localization ◽  
Dependent Cell ◽  
Cell Surface Localization

We found that ENO-1 localizes to caveolae and interacts with caveolin-1 and annexin 2. The association of ENO-1 with caveolar proteins and localization within caveolae are required for ENO-1 cell surface localization and ENO-1-dependent cell migration and invasion.

scholarly journals Modulation of RECK levels in Xenopus A6 cells: effects on MT1-MMP, MMP-2 and pERK levels

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Jessica A. Willson ◽  
Bradley S. Bork ◽  
Carlie A. Muir ◽  
Sashko Damjanovski
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Mammalian Cells ◽  
Mmp Inhibitors ◽  
Erk Activation ◽  
A6 Cells ◽  
A Cell ◽  
Plasmid Transfection

Abstract Background MT1-MMP is a cell-surface enzyme whose regulation of pro-MMP-2 and ERK activation position it as a key facilitator of ECM remodelling and cell migration. These processes are modulated by endogenous MMP inhibitors, such as RECK, a GPI-anchored protein which has been shown to inhibit both MT1-MMP and MMP-2 activity. Our previous studies have revealed a link between MT1-MMP levels, and pro-MMP-2 and ERK activation in mammalian cells, as well as MT1-MMP and RECK co-localization in Xenopus embryos. We here investigated how modulation of RECK would impact MT1-MMP and MMP-2 levels, as well as ERK signalling in Xenopus A6 cells. Results We used a Morpholino approach to knockdown RECK, plasmid transfection to overexpress RECK, and PI-PLC treatment to shed RECK from the cell surface of Xenopus A6 cells. RECK reduction did not alter pERK or MT1-MMP levels, nor MMP-2 activity as measured by zymography; thus RECK-knockdown cells maintained the ability to remodel the ECM. RECK overexpression and PI-PLC treatment both increased ECM remodelling potential through increased MT1-MMP protein and relative MMP-2 activation levels. Conclusions RECK changes that reduce the ability of the cell to remodel the ECM (overexpression and cell surface shedding) are compensated for by increases in MT1-MMP, and MMP-2 levels as seen by zymography.

scholarly journals Cross-talk of Integrin α3β1 and Tissue Factor in Cell Migration

2004 ◽  
Vol 15 (10) ◽  
pp. 4416-4425 ◽  
Author(s):  
Andrea Dorfleutner ◽  
Edith Hintermann ◽  
Takehiko Tarui ◽  
Yoshikazu Takada ◽  
Wolfram Ruf
Keyword(s):  
Cell Migration ◽  
Binding Site ◽  
Tissue Factor ◽  
Extracellular Domain ◽  
Cytoplasmic Domain ◽  
Β1 Integrin ◽  
Laminin 5 ◽  
Integrin Binding Site ◽  
Integrin Ligand ◽  
Integrin Α3β1

In cancer and angiogenesis, coagulation-independent roles of tissue factor (TF) in cell migration are incompletely understood. Immobilized anti-TF extracellular domain antibodies induce cell spreading, but this phenomenon is epitope specific and is not induced by anti-TF 5G9. Spreading on anti-TF is β1 integrin–dependent, indicating functional interactions of the TF extracellular domain 5G9 epitope (a presumed integrin-binding site) and integrins. Recombinant TF extracellular domain supports adhesion of cells expressing αvβ3 or certain β1 integrin heterodimers (α3β1, α4β1, α5β1, α6β1, α9β1) and adhesion is blocked by specific anti-integrin antibodies or mutations in the integrin ligand-binding site. Although several studies have linked TF to cell migration, we here demonstrate that TF specifically regulates α3β1-dependent migration on laminin 5. Expression of TF suppresses α3β1-dependent migration, but only when the TF cytoplasmic domain is not phosphorylated. Suppression of migration can be reversed by 5G9, presumably by disrupting integrin interaction, or by the protease ligand VIIa, known to induce PAR-2–dependent phosphorylation of TF. In both cases, release of α3β1 inhibition is prevented by mutation of critical phosphorylation sites in the TF cytoplasmic domain. Thus, TF influences integrin-mediated migration through cooperative intra- and extracellular interactions and phosphorylation regulates TF's function in cell motility.

scholarly journals Identification of Proteins Associating with Glycosylphosphatidylinositol- Anchored T-Cadherin on the Surface of Vascular Endothelial Cells: Role for Grp78/BiP in T-Cadherin-Dependent Cell Survival

2008 ◽  
Vol 28 (12) ◽  
pp. 4004-4017 ◽  
Author(s):  
Maria Philippova ◽  
Danila Ivanov ◽  
Manjunath B. Joshi ◽  
Emmanouil Kyriakakis ◽  
Katharina Rupp ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Cell Survival ◽  
High Performance ◽  
Vascular Endothelial Cells ◽  
Surface Lipid ◽  
Gaba A ◽  
Dependent Cell ◽  
A Cell ◽  
Cell Surface Signaling

ABSTRACT There is scant knowledge regarding how cell surface lipid-anchored T-cadherin (T-cad) transmits signals through the plasma membrane to its intracellular targets. This study aimed to identify membrane proteins colocalizing with atypical glycosylphosphatidylinositol (GPI)-anchored T-cad on the surface of endothelial cells and to evaluate their role as signaling adaptors for T-cad. Application of coimmunoprecipitation from endothelial cells expressing c-myc-tagged T-cad and high-performance liquid chromatography revealed putative association of T-cad with the following proteins: glucose-related protein GRP78, GABA-A receptor α1 subunit, integrin β3, and two hypothetical proteins, LOC124245 and FLJ32070. Association of Grp78 and integrin β3 with T-cad on the cell surface was confirmed by surface biotinylation and reciprocal immunoprecipitation and by confocal microscopy. Use of anti-Grp78 blocking antibodies, Grp78 small interfering RNA, and coexpression of constitutively active Akt demonstrated an essential role for surface Grp78 in T-cad-dependent survival signal transduction via Akt in endothelial cells. The findings herein are relevant in the context of both the identification of transmembrane signaling partners for GPI-anchored T-cad as well as the demonstration of a novel mechanism whereby Grp78 can influence endothelial cell survival as a cell surface signaling receptor rather than an intracellular chaperone.

scholarly journals Involvement of Cell Surface HSP90 in Cell Migration Reveals a Novel Role in the Developing Nervous System

2004 ◽  
Vol 279 (44) ◽  
pp. 45379-45388 ◽  
Author(s):  
Katerina Sidera ◽  
Martina Samiotaki ◽  
Eleni Yfanti ◽  
George Panayotou ◽  
Evangelia Patsavoudi
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Heat Shock ◽  
Cell Surface ◽  
Antigen Expression ◽  
Mass Spectrometry Analysis ◽  
Rhodamine Phalloidin ◽  
Spectrometry Analysis ◽  
Hsp90 Activity ◽  
Surface Localization

Heat shock protein HSP90 plays important roles in cellular regulation, primarily as a chaperone for a number of key intracellular proteins. We report here that the two HSP90 isoforms, α and β, also localize on the surface of cells in the nervous system and are involved in their migration. A 94-kDa surface antigen, the 4C5 antigen, which was previously shown to be involved in migration processes during development of the nervous system, is shown to be identical to HSP90α using mass spectrometry analysis. This identity is further confirmed by immunoprecipitation experiments and by induction of 4C5 antigen expression in heat shock-treated embryonic rat brain cultures. Moreover, immunocytochemistry on live cerebellar rat cells reveals cell surface localization of both HSP90α and -β. Cell migration from cerebellar and sciatic nerve explants is inhibited by anti-HSP90α and anti-HSP90β antibodies, similarly to the inhibition observed with monoclonal antibody 4C5. Moreover, immunostaining with rhodamine-phalloidin of migrating Schwann cells cultured in the presence of antibodies against both α and β isoforms of HSP90 reveals that HSP90 activity is associated with actin cytoskeletal organization, necessary for lamellipodia formation.

scholarly journals α4β1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells

Blood ◽  
2008 ◽  
Vol 112 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Javier Redondo-Muñoz ◽  
Estefanía Ugarte-Berzal ◽  
José A. García-Marco ◽  
Mercedes Hernández del Cerro ◽  
Philippe E. Van den Steen ◽  
...  
Keyword(s):  
Cell Migration ◽  
B Cells ◽  
Cell Surface ◽  
Lymphocytic Leukemia ◽  
Lymphoid Tissues ◽  
Gelatinase B ◽  
A Cell ◽  
Blocking Antibodies ◽  
Hemopexin Domain ◽  
Cell Chronic Lymphocytic Leukemia

Abstract As B-cell chronic lymphocytic leukemia (B-CLL) progresses, malignant cells extravasate and infiltrate lymphoid tissues. Several molecules, including gelatinase B/MMP-9, contribute to these processes. Although mainly a secreted protease, some MMP-9 is present at the B-CLL cell surface and the function, mode of anchoring, and interactions of this MMP-9 are unknown. Here we show that anti–MMP-9 antibodies immunoprecipitated a 190-kDa CD44v isoform and α4β1 integrin from B-CLL cells, but not from normal B cells. Function-blocking antibodies to α4β1 or CD44, or transfection with specific siRNAs, decreased cell-associated proMMP-9 and increased the secreted form. B-CLL cells attached to and bound proMMP-9 and active MMP-9, and this was inhibited by blocking the expression or function of α4β1 or CD44. The MMP-9 hemopexin domain was critical in these interactions. α4β1 and 190-kDa CD44v (but not CD44H) formed a complex at the cell surface, since they both coimmunoprecipitated with anti-α4, anti-β1, or anti-CD44 antibodies. Immunofluorescence analyses confirmed that α4β1 and CD44v colocalized with MMP-9. Binding of proMMP-9 inhibited B-CLL cell migration, and this required MMP-9 proteolytic activity. Thus, we have identified α4β1 and CD44v as a novel proMMP-9 cell surface docking complex and show that cell-associated MMP-9 may regulate B-CLL cell migration and arrest.

scholarly journals Tyrosine 23 Phosphorylation-Dependent Cell-Surface Localization of Annexin A2 Is Required for Invasion and Metastases of Pancreatic Cancer

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e19390 ◽  
Author(s):  
Lei Zheng ◽  
Kelly Foley ◽  
Lanqing Huang ◽  
Ashley Leubner ◽  
Guanglan Mo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Surface ◽  
Annexin A2 ◽  
Surface Localization ◽  
Dependent Cell ◽  
Cell Surface Localization

scholarly journals PSGL-1 Inhibits the Incorporation of SARS-CoV and SARS-CoV-2 Spike Glycoproteins into Pseudovirions and Impairs Pseudovirus Attachment and Infectivity

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 46
Author(s):  
Sijia He ◽  
Abdul A. Waheed ◽  
Brian Hetrick ◽  
Deemah Dabbagh ◽  
Ivan V. Akhrymuk ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Immune Cells ◽  
Interferon Γ ◽  
Surface Glycoprotein ◽  
Target Cells ◽  
Cell Surface Glycoprotein ◽  
A Cell ◽  
Antiviral Activities ◽  
Hiv 1

P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks pseudovirus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells

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