Nectin spot: a novel type of nectin-mediated cell adhesion apparatus

2016 ◽  
Vol 473 (18) ◽  
pp. 2691-2715 ◽  
Author(s):  
Kiyohito Mizutani ◽  
Yoshimi Takai
Keyword(s):  
Cell Adhesion ◽  
Genetic Disorders ◽  
Cell Polarization ◽  
Membrane Receptors ◽  
Surface Proteins ◽  
Cellular Functions ◽  
The Third ◽  
Ig Superfamily ◽  
Cell Adhesions ◽  
Neural Disorders

Nectins are Ca2+-independent immunoglobulin (Ig) superfamily cell adhesion molecules constituting a family with four members, all of which have three Ig-like loops at their extracellular regions. Nectins play roles in the formation of a variety of cell–cell adhesion apparatuses. There are at least three types of nectin-mediated cell adhesions: afadin- and cadherin-dependent, afadin-dependent and cadherin-independent, and afadin- and cadherin-independent. In addition, nectins trans-interact with nectin-like molecules (Necls) with three Ig-like loops and other Ig-like molecules with one to three Ig-like loops. Furthermore, nectins and Necls cis-interact with membrane receptors and integrins, some of which are associated with the nectin-mediated cell adhesions, and play roles in the regulation of many cellular functions, such as cell polarization, movement, proliferation, differentiation, and survival, co-operatively with these cell surface proteins. The nectin-mediated cell adhesions are implicated in a variety of diseases, including genetic disorders, neural disorders, and cancers. Of the three types of nectin-mediated cell adhesions, the afadin- and cadherin-dependent apparatus has been most extensively investigated, but the examples of the third type of apparatus independent of afadin and cadherin are recently increasing and its morphological and functional properties have been well characterized. We review here recent advances in research on this type of nectin-mediated cell adhesion apparatus, which is named nectin spot.

scholarly journals Immune response of calves inoculated with proteins ofAnaplasma marginale bound to an immunostimulant complex

2013 ◽  
Vol 22 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Marcela Ribeiro Gasparini ◽  
Rafael Felipe da Costa Vieira ◽  
Denise Amaral Gomes do Nascimento ◽  
João Luis Garcia ◽  
Odilon Vidotto ◽  
...  
Keyword(s):  
Immune Response ◽  
Current Knowledge ◽  
Surface Proteins ◽  
Control Group ◽  
Humoral Immune ◽  
The Third ◽  
Additional Testing ◽  
Major Surface Proteins ◽  
Cattle Herds ◽  
Major Surface

Despite our current knowledge of the immunology, pathology, and genetics of Anaplasma marginale, prevention in cattle is currently based on old standbys, including live attenuated vaccines, antibiotic treatment, and maintaining enzootic stability in cattle herds. In the present study, we evaluated the use of an immunostimulant complex (ISCOMATRIX) adjuvant, associated with a pool of recombinant major surface proteins (rMSP1a, rMSP1b, rMSP4 and rMSP5) to improve the humoral immune response triggered in calves mainly by IgG2. Ten calves were divided in three groups: 4 calves were inoculated with the ISCOMATRIX/rMSPs (G1); 2 calves were inoculated with ISCOMATRIX adjuvant (G2); and 4 calves received saline (G3). Three inoculations were administered at 21-day intervals. In G1, the calves showed significant increases in total IgG, IgG1 and IgG2 levels 21 days after the second inoculation, compared to the control group (p < 0.05), and G1 calves remained above the cut-off value 28 days after the third inoculation (p < 0.05). The post-immunized sera from calves in G1 reacted specifically for each of the rMSPs used. In conclusion, the ISCOMATRIX/rMSPs induced antigen-specific seroconversion in calves. Therefore, additional testing to explore the protection induced by rMSPs, both alone and in conjunction with proteins previously identified as subdominant epitopes, is warranted.

scholarly journals Familial hypercholesterolemia: etiopathogenesis, diagnosis, treatment and state of the problem in Ukraine

2019 ◽  
Vol 26 (4) ◽  
pp. 23-31
Author(s):  
O. I. Mitchenko ◽  
V. Y. Romanov ◽  
N. M. Chulaevska ◽  
K. O. Timokhova
Keyword(s):  
Total Cholesterol ◽  
Familial Hypercholesterolemia ◽  
Cholesterol Level ◽  
Total Cholesterol Level ◽  
Genetic Disorders ◽  
Low Density Lipoprotein ◽  
Coronary Vessels ◽  
Density Lipoprotein ◽  
Epidemiological Data ◽  
Membrane Receptors

Familial hypercholesterolemia (FH) is one of the most common, inherited autosomal dominant diseases. Most often, FH is caused by dominant mutation of the gene, responsible for the synthesis of low density lipoprotein (LDL) membrane receptors that remove LDL from the blood plasma. As a result, individuals with a mutation of this gene from birth have a significantly increased level of cholesterol LDL in the blood. FH mediates the accelerated development of cardiovascular disease of atherosclerotic genesis, especially coronary heart disease (CHD), so the level of cardiovascular mortality in the population of such patients is extremely high. The article focuses on the fact that the main threat of these lipid disorders is the early and rapid initiation of atherosclerotic lesions of coronary vessels: in patients with heterozygous FH with a total cholesterol level of 8–15 mmol/l, CHD usually manifests up to 55 and 60 years, whereas in homozygous patients with a total cholesterol level of 12–30 mmol/l, CHD manifests at the start of their life and if left untreated, death occurs by the age of 20 years. The major genetic disorders in familial hypercholesterolemia and the frequency of their detection in the population are characterized. There are definitions of clinical screening options for FH: targeted, opportunistic, universal, cascadic. A comprehensive view of the diagnosis of FH according to the Dutch Lipid Clinic Network (DLCN) is provided. The basic principles of non-medication and three-step medication treatment of FH are presented. The article presents a clinical case of the homozygous FH taking into account the peculiarities of the disease course, the results of laboratory and instrumental studies and step-by-step treatment in the department of dyslipidemia of M.D. Strazhesko Institute of Cardiology of NAMS of Ukraine. The epidemiological data of the Ukrainian population survey on the possible prevalence of FH in Ukraine are presented. The preliminary analysis of the Ukrainian registry of patients with FH as a national fragment of the international ScreenProFH Registry and the European Register EAS-FHSC is provided.

scholarly journals Visualizing the dynamics of exported bacterial proteins with the chemogenetic fluorescent reporter FAST

2020 ◽  
Author(s):  
Yankel Chekli ◽  
Caroline Peron-Cane ◽  
Dario Dell’Arciprete ◽  
Jean-François Allemand ◽  
Chenge Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Listeria Monocytogenes ◽  
Cell Surface ◽  
Bacterial Cell ◽  
Surface Proteins ◽  
Cellular Functions ◽  
Reporter Protein ◽  
Cell Surface Proteins ◽  
Fluorescent Reporter ◽  
Bacterial Proteins

AbstractBacterial proteins exported to the cell surface play key cellular functions. However, despite the interest to study the localization of surface proteins such as adhesins, transporters or hydrolases, monitoring their dynamics in live imaging remains challenging, due to the limited availability of fluorescent probes remaining functional after secretion. In this work, we used the Escherichia coli intimin and the Listeria monocytogenes InlB invasin as surface exposed scaffolds fused with the recently developed chemogenetic fluorescent reporter protein FAST. Using both membrane permeant (HBR-3,5DM) and non-permeant (HBRAA-3E) fluorogens that fluoresce upon binding to FAST, we demonstrated that fully functional FAST can be exposed at the cell surface and specifically tagged on the external side of the bacterial envelop in both diderm and monoderm bacteria. Our work opens new avenues to study of the organization and dynamics of the bacterial cell surface proteins.

scholarly journals Paxillin-Kinase-Linker Tyrosine Phosphorylation Regulates Directional Cell Migration

2009 ◽  
Vol 20 (22) ◽  
pp. 4706-4719 ◽  
Author(s):  
Jianxin A. Yu ◽  
Nicholas O. Deakin ◽  
Christopher E. Turner
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Wound Repair ◽  
Cell Polarization ◽  
Dependent Manner ◽  
Directed Cell Migration ◽  
Focal Adhesion Protein ◽  
Directional Cell Migration

Directed cell migration requires the coordination of growth factor and cell adhesion signaling and is of fundamental importance during embryonic development, wound repair, and pathological conditions such as tumor metastasis. Herein, we demonstrate that the ArfGAP, paxillin-kinase-linker (PKL/GIT2), is tyrosine phosphorylated in response to platelet-derived growth factor (PDGF) stimulation, in an adhesion dependent manner and is necessary for directed cell migration. Using a combination of pharmacological inhibitors, knockout cells and kinase mutants, FAK, and Src family kinases were shown to mediate PDGF-dependent PKL tyrosine phosphorylation. In fibroblasts, expression of a PKL mutant lacking the principal tyrosine phosphorylation sites resulted in loss of wound-induced cell polarization as well as directional migration. PKL phosphorylation was necessary for PDGF-stimulated PKL binding to the focal adhesion protein paxillin and expression of paxillin or PKL mutants defective in their respective binding motifs recapitulated the polarization defects. RNA interference or expression of phosphorylation mutants of PKL resulted in disregulation of PDGF-stimulated Rac1 and PAK activities, reduction of Cdc42 and Erk signaling, as well as mislocalization of βPIX. Together these studies position PKL as an integral component of growth factor and cell adhesion cross-talk signaling, controlling the development of front–rear cell polarity and directional cell migration.

scholarly journals A Novel Class of Ectomycorrhiza-Regulated Cell Wall Polypeptides in Pisolithus tinctorius

1999 ◽  
Vol 12 (10) ◽  
pp. 862-871 ◽  
Author(s):  
Pascal Laurent ◽  
Catherine Voiblet ◽  
Denis Tagu ◽  
Dulcinéia de Carvalho ◽  
Uwe Nehls ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Adhesion ◽  
Polyacrylamide Gel Electrophoresis ◽  
State Level ◽  
Root Surface ◽  
Pisolithus Tinctorius ◽  
Surface Proteins ◽  
Ectomycorrhizal Symbiosis ◽  
Fungal Cell ◽  
Fungal Hyphae

Development of the ectomycorrhizal symbiosis leads to the aggregation of fungal hyphae to form the mantle. To identify cell surface proteins involved in this developmental step, changes in the biosynthesis of fungal cell wall proteins were examined in Eucalyptus globulus-Pisolithus tinctorius ectomycorrhizas by two-dimensional polyacrylamide gel electrophoresis. Enhanced synthesis of several immunologically related fungal 31- and 32-kDa polypeptides, so-called symbiosis-regulated acidic polypeptides (SRAPs), was observed. Peptide sequences of SRAP32d were obtained after trypsin digestion. These peptides were found in the predicted sequence of six closely related fungal cDNAs coding for ectomycorrhiza up-regulated transcripts. The PtSRAP32 cDNAs represented about 10% of the differentially expressed cDNAs in ectomycorrhiza and are predicted to encode alanine-rich proteins of 28.2 kDa. There are no sequence homologies between SRAPs and previously identified proteins, but they contain the Arg-Gly-Asp (RGD) motif found in cell-adhesion proteins. SRAPs were observed on the hyphal surface by immunoelectron microscopy. They were also found in the host cell wall when P. tinctorius attached to the root surface. RNA blot analysis showed that the steady-state level of PtSRAP32 transcripts exhibited a drastic up-regulation when fungal hyphae form the mantle. These results suggest that SRAPs may form part of a cell-cell adhesion system needed for aggregation of hyphae in ectomycorrhizas.

scholarly journals Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability

2012 ◽  
Vol 198 (2) ◽  
pp. 251-263 ◽  
Author(s):  
Enora Moutin ◽  
Fabrice Raynaud ◽  
Jonathan Roger ◽  
Emilie Pellegrino ◽  
Vincent Homburger ◽  
...  
Keyword(s):  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Membrane Receptors ◽  
Physical Interaction ◽  
Scaffolding Proteins ◽  
Cellular Functions ◽  
Electrophysiological Recordings ◽  
Living Neurons ◽  
Activity Dependent

Scaffolding proteins interact with membrane receptors to control signaling pathways and cellular functions. However, the dynamics and specific roles of interactions between different components of scaffold complexes are poorly understood because of the dearth of methods available to monitor binding interactions. Using a unique combination of single-cell bioluminescence resonance energy transfer imaging in living neurons and electrophysiological recordings, in this paper, we depict the role of glutamate receptor scaffold complex remodeling in space and time to control synaptic transmission. Despite a broad colocalization of the proteins in neurons, we show that spine-confined assembly/disassembly of this scaffold complex, physiologically triggered by sustained activation of synaptic NMDA (N-methyl-d-aspartate) receptors, induces physical association between ionotropic (NMDA) and metabotropic (mGlu5a) synaptic glutamate receptors. This physical interaction results in an mGlu5a receptor–mediated inhibition of NMDA currents, providing an activity-dependent negative feedback loop on NMDA receptor activity. Such protein scaffold remodeling represents a form of homeostatic control of synaptic excitability.

scholarly journals Computational design of orthogonal membrane receptor-effector switches for rewiring signaling pathways

2018 ◽  
Vol 115 (27) ◽  
pp. 7051-7056 ◽  
Author(s):  
M. Young ◽  
T. Dahoun ◽  
B. Sokrat ◽  
C. Arber ◽  
K. M. Chen ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
High Specificity ◽  
Computational Design ◽  
Membrane Receptor ◽  
Membrane Receptors ◽  
Cellular Functions ◽  
Hierarchical Code

Membrane receptors regulate numerous intracellular functions. However, the molecular underpinnings remain poorly understood because most receptors initiate multiple signaling pathways through distinct interaction interfaces that are structurally uncharacterized. We present an integrated computational and experimental approach to model and rationally engineer membrane receptor-intracellular protein systems signaling with novel pathway selectivity. We targeted the dopamine D2 receptor (D2), a G-protein–coupled receptor (GPCR), which primarily signals through Gi, but triggers also the Gq and beta-arrestin pathways. Using this approach, we designed orthogonal D2–Gi complexes, which coupled with high specificity and triggered exclusively the Gi-dependent signaling pathway. We also engineered an orthogonal chimeric D2–Gs/i complex that rewired D2 signaling from a Gi-mediated inhibitory into a Gs-dependent activating pathway. Reinterpreting the evolutionary history of GPCRs in light of the designed proteins, we uncovered an unforeseen hierarchical code of GPCR–G-protein coupling selectivity determinants. The results demonstrate that membrane receptor–cytosolic protein systems can be rationally engineered to regulate mammalian cellular functions. The method should prove useful for creating orthogonal molecular switches that redirect signals at the cell surface for cell-engineering applications.

Neural cell adhesion molecules during embryonic induction and development of the kidney

Development ◽  
1988 ◽  
Vol 102 (4) ◽  
pp. 749-761 ◽  
Author(s):  
G. Klein ◽  
M. Langegger ◽  
C. Goridis ◽  
P. Ekblom
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Kidney Development ◽  
Neural Cell ◽  
Cell Polarization ◽  
Embryonic Induction ◽  
Neural Cell Adhesion Molecules ◽  
Short Period ◽  
Neural Cell Adhesion

The neural cell adhesion molecules (N-CAM) are a family of related glycoproteins with Mr of 180, 140 and 120 × 10(3) (180K etc.). In the embryo, they are often highly sialylated and migrate as a diffuse band of 170–250K. N-CAM are found in non-neural tissues and we have now studied the expression of N-CAM in the developing mouse kidney. During kidney development, a unique conversion of a mesenchyme to an epithelium occurs and it is thought that this is mediated by an increase in cell adhesivity. By immunofluorescence, we show that N-CAM is present already at onset of kidney development on the cells of the uninduced nephrogenic mesenchyme. After induction, when the cells convert into an epithelium, they lose N-CAM gradually and instead begin to express uvomorulin, another primary CAM. By using an organ culture model, we could rather precisely show that N-CAM and uvomorulin are coexpressed for a short period, but, when epithelial cell polarization is evident, only uvomorulin is present on the epithelium, whereas N-CAM is confined to the surrounding mesenchyme. Immunoblotting for N-CAM revealed that the ‘embryonic’ form of N-CAM, the broad 170–250K band was not present in the embryonic kidney, which instead expressed the three distinct 180K, 140K and 120K bands typical of adult neurones. The 180K and 140K bands were gradually lost during development and were no longer detectable in adult kidneys. By using an N-CAM cDNA, we detected three different mRNAs of 7.4, 6.7 and 4.3 kb in the developing kidney, but this expression was restricted to the embryonic and early postnatal stages. No transcripts were detectable in adult kidneys. The studies do not support the hypothesis that N-CAM expression in the kidney is turned on by embryonic induction. Rather, we suggest that N-CAM are important adhesives for the predetermined, but not yet induced, nephrogenic mesenchyme.

Expression and adhesive activity of SC1, an Ig superfamily cell adhesion molecule, in sporadic nephroblastomas of chicken

2006 ◽  
Author(s):  
Yasuhiro Tsukamoto ◽  
Takashi Namikawa ◽  
Ryouta Tatesaki ◽  
Takao Kotani ◽  
Hideaki Tanaka
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Ig Superfamily
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