scholarly journals Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9177
Author(s):  
Jing Yang Tee ◽  
Alan Mackay-Sim
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Brain Development ◽  
Schizophrenia Patient ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Dependent Manner ◽  
Plastic Substrates ◽  
Olfactory Cells ◽  
And Control

Cell migration is critical for brain development and linked to several neurodevelopmental disorders, including schizophrenia. We have shown previously that cell migration is dysregulated in olfactory neural stem cells from people with schizophrenia. Although they moved faster than control cells on plastic substrates, patient cells were insensitive to regulation by extracellular matrix proteins, which increase the speeds of control cells. As well as speed, cell migration is also described by directional persistence, the straightness of movement. The aim of this study was to determine whether directional persistence is dysregulated in schizophrenia patient cells and whether it is modified on extracellular matrix proteins. Directional persistence in patient-derived and control-derived olfactory cells was quantified from automated live-cell imaging of migrating cells. On plastic substrates, patient cells were more persistent than control cells, with straighter trajectories and smaller turn angles. On most extracellular matrix proteins, persistence increased in patient and control cells in a concentration-dependent manner, but patient cells remained more persistent. Patient cells therefore have a subtle but complex phenotype in migration speed and persistence on most extracellular matrix protein substrates compared to control cells. If present in the developing brain, this could lead to altered brain development in schizophrenia.

Von Willebrand Factor Binds to the Endothelial Growth Factor Angiopoietin-2 Both within Endothelial Cells and Upon Release From Weibel Palade Bodies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 698-698 ◽  
Author(s):  
Thomas A J Mckinnon ◽  
Richard D Starke ◽  
Kushani Ediriwickrema ◽  
Anna Maria Randi ◽  
Michael Laffan
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Dependent Manner ◽  
Platelet Receptor ◽  
Angiopoietin 2 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 698 Von Willebrand Factor (VWF) is a large multimeric plasma glycoprotein essential for homeostasis, also involved in inflammation and angiogenesis. The majority of VWF is synthesised by endothelial cells (EC) and is either constitutively secreted or stored in Weibel-Palade bodies (WPB), ready to be released in response to endothelial stimulation. Several studies have shown that formation of WPB is dependent on the presence of VWF, and deletion of VWF in human umbilical vein EC (HUVEC) results in loss of WPB. Amongst the other proteins shown to co-localise to WPB is angiopoietin-2 (Ang2), a ligand of the receptor tyrosine kinase Tie-2. Ang2 regulates endothelial cell survival, vascular stability and maturation, by destabilizing quiescent endothelium and facilitating the response to inflammatory and angiogenic stimuli. VWF is required for storage of Ang2, and release of Ang-2 from EC is increased in VWF-deficient HUVEC. Recently, we have shown that VWF itself regulates angiogenesis, raising the hypothesis that some of the angiogenic activity of VWF may be mediated by Ang-2. In the present study we investigated the interaction between Ang2 and VWF. Binding analysis demonstrated that recombinant human Ang2 bound to purified plasma-derived VWF in a pH and calcium dependent manner, with optimal binding occurring at pH 6.5 and 10mM calcium, indicative of binding within the Golgi body. Generation of binding isotherms established that Ang2 bound to VWF with high affinity (KD∼3nM); furthermore binding affinity was not dependent on VWF conformation. Using an array of VWF constructs we determined that Ang2 bound predominantly to the VWF A1 domain, which also contains binding sites to the platelet receptor GPIb and extracellular matrix proteins. Co-immunoprecipitation experiments performed on TNFα- and ionomycin-stimulated HUVECs, to induce WPB exocytosis, confirmed that a portion of Ang2 remained bound to secreted VWF. Moreover, immunofluorescence staining of histamine-stimulated HUVECs to induce VWF release demonstrated the presence of Ang2 on VWF strings secreted from ECs. Finally we demonstrated that Ang2 bound to VWF was still able to interact with Tie-2. These data demonstrate that binding of Ang2 to VWF occurs within the cell; we propose that this is the mechanism mediating storage of Ang2 in WPB. Moreover, the finding that the Ang2-VWF interaction is preserved following secretion raises the intriguing possibility VWF may affect Ang2 function, possibly by localising Ang2 to the Tie 2 receptor under the shear forces experienced in flowing blood. Similarly, Ang-2 binding to VWF may modulate its interaction with receptors and extracellular matrix proteins, and ultimately influence the role of VWF in the angiogenic processes. Disclosures: No relevant conflicts of interest to declare.

Role of high molecular weight extracellular matrix proteins in glioma cell migration

1997 ◽  
Vol 23 (2) ◽  
pp. 102-112 ◽  
Author(s):  
R. Mahesparan ◽  
B. B. Tysnes ◽  
K. Edvardsen ◽  
H. K. Haugeland ◽  
I. Garcia Cabrera ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
High Molecular Weight ◽  
Glioma Cell ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Glioma Cell Migration

Promotion of Tumor Cell Migration by Extracellular Matrix Proteins in Human Pancreatic Cancer

Pancreas ◽  
2009 ◽  
Vol 38 (7) ◽  
pp. 804-810 ◽  
Author(s):  
Eduard Ryschich ◽  
Akmal Khamidjanov ◽  
Vachtang Kerkadze ◽  
Markus W. Büchler ◽  
Margot Zöller ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Tumor Cell ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Human Pancreatic Cancer ◽  
Tumor Cell Migration

Extracellular matrix proteins in intrathymic T-cell migration and differentiation?

1993 ◽  
Vol 14 (4) ◽  
pp. 158-161 ◽  
Author(s):  
Wilson Savino ◽  
Dea Maria S. Villa-Verde ◽  
Joseli Lannes-Vieira
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
T Cell ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
T Cell Migration

Role of Mycoplasma pneumoniae glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in mediating interactions with the human extracellular matrix

Microbiology ◽  
2011 ◽  
Vol 157 (8) ◽  
pp. 2328-2338 ◽  
Author(s):  
Roger Dumke ◽  
Marius Hausner ◽  
Enno Jacobs
Keyword(s):  
Extracellular Matrix ◽  
Mycoplasma Pneumoniae ◽  
Extracellular Matrix Proteins ◽  
Polyclonal Antiserum ◽  
Glycolytic Enzymes ◽  
Matrix Proteins ◽  
Dependent Manner ◽  
Human Respiratory Tract ◽  
Concentration Dependent Manner ◽  
Micro Organisms

In different, phylogenetically unrelated micro-organisms, glycolytic enzymes play a dual role. In the cytosol they are involved in metabolic reactions whereas the surface-localized fraction of the enzymes contributes to adhesion and virulence. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a typical member of this group of multifunctional proteins. In this study, we characterized the GAPDH of Mycoplasma pneumoniae, a common pathogen of the human respiratory mucosa. Full-length GAPDH of M. pneumoniae was successfully expressed and used to produce a polyclonal antiserum. By immunofluorescence, colony blot and ELISA experiments with different fractions of the M. pneumoniae proteins, GAPDH was demonstrated to be present in the cytosol and at even higher concentrations at the surface of mycoplasmas. Nevertheless, antibodies against recombinant GAPDH were not detected in sera of immunized animals or of patients with confirmed M. pneumoniae infection. Recombinant GAPDH bound to different human cell lines in a concentration-dependent manner, and binding was inhibited by specific anti-GAPDH serum. In contrast, this antiserum did not significantly influence the adherence of M. pneumoniae to HeLa cells. When different human extracellular matrix proteins were tested in Western blot assays, GAPDH bound to fibrinogen. The results showed that the GAPDH of M. pneumoniae is a member of the family of cytosol-localized glycolytic enzymes, which also occur at the surface of the bacterium, and mediates interactions with the extracellular matrix proteins of the human host. Thus, the surface-exposed fraction of GAPDH may be a factor that contributes to the successful colonization of the human respiratory tract by M. pneumoniae.

Cell Migration and Polarity on Microfabricated Gradients of Extracellular Matrix Proteins

Langmuir ◽  
2006 ◽  
Vol 22 (9) ◽  
pp. 4250-4258 ◽  
Author(s):  
Rico C. Gunawan ◽  
Jonathan Silvestre ◽  
H. Rex Gaskins ◽  
Paul J. A. Kenis ◽  
Deborah E. Leckband
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins

scholarly journals Purification and Partial Characterization of a Paracoccidioides brasiliensis Protein with Capacity To Bind to Extracellular Matrix Proteins

2005 ◽  
Vol 73 (4) ◽  
pp. 2486-2495 ◽  
Author(s):  
Angel González ◽  
Beatriz L. Gómez ◽  
Soraya Diez ◽  
Orville Hernández ◽  
Angela Restrepo ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Paracoccidioides Brasiliensis ◽  
Sodium Dodecyl ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Yeast Cells ◽  
Extracellular Matrix Protein ◽  
Dependent Manner ◽  
Fungal Propagules

ABSTRACT Microorganisms adhere to extracellular matrix proteins by means of their own surface molecules. Paracoccidioides brasiliensis conidia have been shown to be capable of interacting with extracellular matrix proteins. We aimed at determining the presence of fungal proteins that could interact with extracellular matrix protein and, if found, attempt their purification and characterization. Various extracts were prepared from P. brasiliensis mycelial and yeast cultures (total homogenates, β-mercaptoethanol, and sodium dodecyl sulfate [SDS] extracts) and analyzed by ligand affinity assays with fibronectin, fibrinogen and laminin. Two polypeptides were detected in both fungal forms. SDS extracts that interacted with all the extracellular matrix protein were tested; their molecular masses were 19 and 32 kDa. Analysis of the N-terminal amino acid sequence of the purified 32-kDa mycelial protein showed substantial homology with P. brasiliensis, Histoplasma capsulatum, and Neurospora crassa hypothetical proteins. Additionally, a monoclonal antibody (MAb) produced against this protein recognized the 32-kDa protein in the SDS extracts of both fungal forms for immunoblot. Immunofluorescence analysis revealed that this MAb reacted not only with mycelia and yeast cells, but also with conidia, indicating that this protein was shared by the three fungal propagules. By immunoelectron microscopy, this protein was detected in the cell walls and in the cytoplasm. Both the 32-kDa purified protein and MAb inhibited the adherence of conidia to the three extracellular matrix proteins in a dose-dependent manner. These findings demonstrate the presence of two polypeptides capable of interacting with extracellular matrix proteins on the surface of P. brasiliensis propagules, indicating that there may be common receptors for laminin, fibronectin, and fibrinogen. These proteins would be crucial for initial conidial adherence and perhaps also in dissemination of paracoccidioidomycosis.

scholarly journals The Major Pilin Subunit of the AAF/II Fimbriae from Enteroaggregative Escherichia coli Mediates Binding to Extracellular Matrix Proteins

2008 ◽  
Vol 76 (10) ◽  
pp. 4378-4384 ◽  
Author(s):  
Mauricio J. Farfan ◽  
Keith G. Inman ◽  
James P. Nataro
Keyword(s):  
Escherichia Coli ◽  
Extracellular Matrix ◽  
Extracellular Matrix Proteins ◽  
Prototype Strain ◽  
Matrix Proteins ◽  
Dependent Manner ◽  
T84 Cells ◽  
Cell Monolayers ◽  
Type Iv ◽  
Pilin Gene

ABSTRACT Enteroaggregative Escherichia coli (EAEC) adherence to human intestinal tissue is mediated by aggregative adherence fimbriae (AAF); however, the receptors involved in EAEC adherence remain uncharacterized. Adhesion to extracellular matrix proteins is commonly observed among enteric pathogens, so we addressed the hypothesis that EAEC may bind to extracellular matrix proteins commonly found in the intestine. We found that EAEC prototype strain 042 adhered more abundantly to surfaces that were precoated with the extracellular matrix proteins fibronectin, laminin, and type IV collagen. Differences in fibronectin binding of almost 2 orders of magnitude were observed between EAEC 042 and a mutant in the AAF/II major pilin gene, aafA. Purified AafA, refolded as a donor strand complementation construct, bound fibronectin in a dose-dependent manner. Addition of fibronectin to the apical surfaces of polarized T84 cell monolayers augmented EAEC 042 adherence, and this effect required expression of aafA. Finally, increased bacterial adherence was observed when apical secretion of fibronectin was induced by adenosine in polarized T84 cells. Binding to fibronectin may contribute to colonization of the gastrointestinal tract by EAEC.

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