scholarly journals Syntenin: PDZ Protein Regulating Signaling Pathways and Cellular Functions

2019 ◽  
Vol 20 (17) ◽  
pp. 4171 ◽  
Author(s):  
Tadayuki Shimada ◽  
Shin Yasuda ◽  
Hiroko Sugiura ◽  
Kanato Yamagata
Keyword(s):  
Cell Types ◽  
Pdz Domains ◽  
Cellular Functions ◽  
Peptide Motifs ◽  
Neuronal Synapses ◽  
Zonula Occludens ◽  
Exosome Biogenesis ◽  
Discs Large ◽  
Pdz Protein ◽  
Zonula Occludens 1

Syntenin is an adaptor-like molecule that has two adjacent tandem postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ) domains. The PDZ domains of syntenin recognize multiple peptide motifs with low to moderate affinity. Many reports have indicated interactions between syntenin and a plethora of proteins. Through interactions with various proteins, syntenin regulates the architecture of the cell membrane. As a result, increases in syntenin levels induce the metastasis of tumor cells, protrusion along the neurite in neuronal cells, and exosome biogenesis in various cell types. Here, we review the updated data that support various roles for syntenin in the regulation of neuronal synapses, tumor cell invasion, and exosome control.

scholarly journals Displacement of basolateral Bazooka/PAR-3 by regulated transport and dispersion during epithelial polarization in Drosophila

2012 ◽  
Vol 23 (22) ◽  
pp. 4465-4471 ◽  
Author(s):  
R. F. Andrew McKinley ◽  
Tony J. C. Harris
Keyword(s):  
Caenorhabditis Elegans ◽  
Transport Mechanism ◽  
Basolateral Membrane ◽  
Adherens Junction ◽  
Pdz Domains ◽  
Zonula Occludens ◽  
Epithelial Development ◽  
Discs Large ◽  
Zonula Occludens 1 ◽  
Acting In Concert

Polarity landmarks guide epithelial development. In the early Drosophila ectoderm, the scaffold protein Bazooka (Drosophila PAR-3) forms apicolateral landmarks to direct adherens junction assembly. However, it is unclear how Bazooka becomes polarized. We report two mechanisms acting in concert to displace Bazooka from the basolateral membrane. As cells form during cellularization, basally localized Bazooka undergoes basal-to-apical transport. Bazooka requires its three postsynaptic density 95, discs large, zonula occludens-1 (PDZ) domains to engage the transport mechanism, but with the PDZ domains deleted, basolateral displacement still occurs by gastrulation. Basolateral PAR-1 activity appears to act redundantly with the transport mechanism. Knockdown of PAR-1 sporadically destabilizes cellularization furrows, but basolateral displacement of Bazooka still occurs by gastrulation. In contrast, basolateral Bazooka displacement is blocked with disruption of both the transport mechanism and phosphorylation by PAR-1. Thus Bazooka is polarized through a combination of transport and PAR-1–induced dispersion from basolateral membranes. Our work complements recent findings in Caenorhabditis elegans and thus suggests the coupling of transport and dispersion is a common protein polarization strategy.

scholarly journals Distance-dependent adhesion of vascular cells on biofunctionalized nanostructures

2017 ◽  
Vol 3 (2) ◽  
pp. 683-686
Author(s):  
Sarah Biela ◽  
Britta Striegl ◽  
Kerstin Frey ◽  
Joachim P. Spatz ◽  
Ralf Kemkemer
Keyword(s):  
Extracellular Matrix ◽  
Vascular Tissue ◽  
Cell Types ◽  
Cell Interaction ◽  
Vascular Cells ◽  
Cellular Functions ◽  
Ligand Interaction ◽  
Nanostructured Surfaces ◽  
Peptide Motifs ◽  
Cell Cell

AbstractCell-cell and cell-extracellular matrix (ECM) adhesion regulates fundamental cellular functions and is crucial for cell-material contact. Adhesion is influenced by many factors like affinity and specificity of the receptor-ligand interaction or overall ligand concentration and density. To investigate molecular details of cell-ECM and cadherins (cell-cell) interaction in vascular cells functional nanostructured surfaces were used Ligand-functionalized gold nanoparticles (AuNPs) with 6-8 nm diameter, are precisely immobilized on a surface and separated by non-adhesive regions so that individual integrins or cadherins can specifically interact with the ligands on the AuNPs. Using 40 nm and 90 nm distances between the AuNPs and functionalized either with peptide motifs of the extracellular matrix (RGD or REDV) or vascular endothelial-cadherins (VEC), the influence of distance and ligand specificity on spreading and adhesion of endothelial cells (ECs) and smooth muscle cells (SMCs) was investigated. We demonstrate that RGD-dependent adhesion of vascular cells is similar to other cell types and that the distance dependence for integrin binding to ECM-peptides is also valid for the REDV motif. VEC-ligands decrease adhesion significantly on the tested ligand distances. These results may be helpful for future improvements in vascular tissue engineering and for development of implant surfaces.

scholarly journals Identification of PDZ Domain Containing Proteins Interacting with 1.2 and PMCA4b

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Doreen Korb ◽  
Priscilla Y. Tng ◽  
Vladimir M. Milenkovic ◽  
Nadine Reichhart ◽  
Olaf Strauss ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Pdz Domains ◽  
Hek 293 ◽  
Zonula Occludens ◽  
C Terminus ◽  
293 Cells ◽  
Interaction Partners ◽  
Voltage Dependent ◽  
Interaction Domains ◽  
Zonula Occludens 1

PDZ (PSD-95/Disc large/Zonula occludens-1) protein interaction domains bind to cytoplasmic protein C-termini of transmembrane proteins. In order to identify new interaction partners of the voltage-gated L-type Ca2+ channel 1.2 and the plasma membrane Ca2+ ATPase 4b (PMCA4b), we used PDZ domain arrays probing for 124 PDZ domains. We confirmed this by GST pull-downs and immunoprecipitations. In PDZ arrays, strongest interactions with 1.2 and PMCA4b were found for the PDZ domains of SAP-102, MAST-205, MAGI-1, MAGI-2, MAGI-3, and ZO-1. We observed binding of the 1.2 C-terminus to PDZ domains of NHERF1/2, Mint-2, and CASK. PMCA4b was observed to interact with Mint-2 and its known interactions with Chapsyn-110 and CASK were confirmed. Furthermore, we validated interaction of 1.2 and PMCA4b with NHERF1/2, CASK, MAST-205 and MAGI-3 via immunoprecipitation. We also verified the interaction of 1.2 and nNOS and hypothesized that nNOS overexpression might reduce Ca2+ influx through 1.2. To address this, we measured Ca2+ currents in HEK 293 cells co-expressing 1.2 and nNOS and observed reduced voltage-dependent 1.2 activation. Taken together, we conclude that 1.2 and PMCA4b bind promiscuously to various PDZ domains, and that our data provides the basis for further investigation of the physiological consequences of these interactions.

scholarly journals Protein Kinase D Intracellular Localization and Activity Control Kinase D-interacting Substrate of 220-kDa Traffic through a Postsynaptic Density-95/Discs Large/Zonula Occludens-1-binding Motif

2006 ◽  
Vol 281 (27) ◽  
pp. 18888-18900 ◽  
Author(s):  
Lucía Sánchez-Ruiloba ◽  
Noemí Cabrera-Poch ◽  
María Rodríguez-Martínez ◽  
Celia López-Menéndez ◽  
Roberto Martín Jean-Mairet ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Intracellular Localization ◽  
Postsynaptic Density ◽  
Protein Kinase D ◽  
Binding Motif ◽  
Zonula Occludens ◽  
Discs Large ◽  
Zonula Occludens 1

scholarly journals PDZ interactions regulate rapid turnover of the scaffolding protein EBP50 in microvilli

2012 ◽  
Vol 198 (2) ◽  
pp. 195-203 ◽  
Author(s):  
Damien Garbett ◽  
Anthony Bretscher
Keyword(s):  
Cell Extract ◽  
Scaffolding Protein ◽  
Scaffolding Proteins ◽  
Pdz Domains ◽  
Kinase C ◽  
Zonula Occludens ◽  
Discs Large ◽  
Specific Proteins

Scaffolding proteins containing PDZ (postsynaptic density 95/discs large/zonula occludens-1) domains are believed to provide relatively stable linkages between components of macromolecular complexes and in some cases to bridge to the actin cytoskeleton. The microvillar scaffolding protein EBP50 (ERM-binding phosphoprotein of 50 kD), consisting of two PDZ domains and an ezrin-binding site, retains specific proteins in microvilli and is necessary for microvillar biogenesis. Our analysis of the dynamics of microvillar proteins in vivo indicated that ezrin and microvillar membrane proteins had dynamics consistent with actin treadmilling and microvillar lifetimes. However, EBP50 was highly dynamic, turning over within seconds. EBP50 turnover was reduced by mutations that inactivate its PDZ domains and was enhanced by protein kinase C phosphorylation. Using a novel in vitro photoactivation fluorescence assay, the EBP50–ezrin interaction was shown to have a slow off-rate that was dramatically enhanced in a PDZ-regulated manner by addition of cell extract to near in vivo levels. Thus, the linking of relatively stable microvillar components can be mediated by surprisingly dynamic EBP50, a finding that may have important ramifications for other scaffolding proteins.

scholarly journals ZO-1- and ZO-2-Dependent Integration of Myosin-2 to Epithelial Zonula Adherens

2008 ◽  
Vol 19 (9) ◽  
pp. 3801-3811 ◽  
Author(s):  
Yuji Yamazaki ◽  
Kazuaki Umeda ◽  
Masami Wada ◽  
Shigeyuki Nada ◽  
Masato Okada ◽  
...  
Keyword(s):  
Cell Sheet ◽  
Resonance Energy Transfer ◽  
Rho Kinase ◽  
Resonance Energy ◽  
Linear Arrangement ◽  
Zonula Occludens ◽  
Discs Large ◽  
Epithelial Sheet ◽  
Zonula Occludens 1 ◽  
E Cadherin

For the zonula adherens (ZA) to be established by linear arrangement of adherens junctions (AJs) in epithelial sheet cells, critical for the epithelial cell sheet formation and intercellular barrier function, myosin-2 is supposedly integrated into the ZA with the result of overlapping localization of E-cadherin/actin/myosin-2. Here, we immunofluorescently showed that myosin-2 failed to be integrated into the ZA in cultured epithelial-type ZO1(ko)/2(kd) Eph4 cells lacking ZO-1 and -2 (zonula occludens-1 and -2) by knockout and knockdown, respectively. Instead, a linearized but fragmented arrangement of AJs was formed in the way that it was positive for E-cadherin/actin, but negative for myosin-2 (designated prezonula-AJ). Transfection of full-length ZO-1 or ZO-2, or ZO-1 lacking its PDZ (PSD-95/discs large/zonula occludens-1)-1/2 domains (but not one lacking PDZ-1/2/3) into ZO1(ko)/2(kd) Eph4 cells restored the junctional integration of myosin-2 with prezonula-AJ to establish the ZA. Transfection of dominant-active RhoA or Rho-kinase (ROCK), as well as administration of lysophosphatidic acid or Y27632, which activates RhoA or inhibits ROCK, respectively, suggested that RhoA regulated the junctional integration of myosin-2 into ZA in a manner such that ROCK played a necessary but not-sufficient role. Fluorescence resonance energy transfer analyses revealed that spatiotemporal Rho-activation occurred in a ZO-1/2–dependent way to establish ZA from primordial forms in epithelial cells.

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