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 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 Basolateral Localization of the Caenorhabditis elegans Epidermal Growth Factor Receptor in Epithelial Cells by the PDZ Protein LIN-10

1999 ◽  
Vol 10 (6) ◽  
pp. 2087-2100 ◽  
Author(s):  
Charles W. Whitfield ◽  
Claire Bénard ◽  
Tom Barnes ◽  
S. Hekimi ◽  
Stuart K. Kim
Keyword(s):  
Plasma Membrane ◽  
Caenorhabditis Elegans ◽  
Epithelial Cells ◽  
Egf Receptor ◽  
Basolateral Membrane ◽  
Growth Factor Receptor ◽  
Pdz Domains ◽  
Membrane Domain ◽  
Interaction Domains ◽  
New Gene

In Caenorhabditis elegans, the EGF receptor (encoded by let-23) is localized to the basolateral membrane domain of the epithelial vulval precursor cells, where it acts through a conserved Ras/MAP kinase signaling pathway to induce vulval differentiation. lin-10 acts in LET-23 receptor tyrosine kinase basolateral localization, because lin-10mutations result in mislocalization of LET-23 to the apical membrane domain and cause a signaling defective (vulvaless) phenotype. We demonstrate that the previous molecular identification oflin-10 was incorrect, and we identify a new gene corresponding to the lin-10 genetic locus.lin-10 encodes a protein with regions of similarity to mammalian X11/mint proteins, containing a phosphotyrosine-binding and two PDZ domains. A nonsense lin-10 allele that truncates both PDZ domains only partially reduces lin-10 gene activity, suggesting that these protein interaction domains are not essential for LIN-10 function in vulval induction. Immunocytochemical experiments show that LIN-10 is expressed in vulval epithelial cells and in neurons. LIN-10 is present at low levels in the cytoplasm and at the plasma membrane and at high levels at or near the Golgi. LIN-10 may function in secretion of LET-23 to the basolateral membrane domain, or it may be involved in tethering LET-23 at the basolateral plasma membrane once it is secreted.

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

Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and l-glutamine

2005 ◽  
Vol 289 (2) ◽  
pp. G367-G375 ◽  
Author(s):  
S. Basuroy ◽  
P. Sheth ◽  
C. M. Mansbach ◽  
R. K. Rao
Keyword(s):  
Tight Junction ◽  
Tyrosine Phosphorylation ◽  
Colonic Mucosa ◽  
Adherens Junction ◽  
Toxic Metabolite ◽  
Protein Tyrosine ◽  
Zonula Occludens ◽  
Increased Risk ◽  
Zonula Occludens 1 ◽  
E Cadherin

Acetaldehyde, a toxic metabolite of ethanol oxidation, is suggested to play a role in the increased risk for gastrointestinal cancers in alcoholics. In the present study, the effect of acetaldehyde on tyrosine phosphorylation, immmunofluorescence localization, and detergent-insoluble fractions of the tight junction and the adherens junction proteins was determined in the human colonic mucosa. The role of EGF and l-glutamine in prevention of acetaldehyde-induced effects was also evaluated. Acetaldehyde reduced the protein tyrosine phosphatase activity, thereby increasing the tyrosine phosphorylation of occludin, E-cadherin, and β-catenin. The levels of occludin, zonula occludens-1, E-cadherin, and β-catenin in detergent-insoluble fractions were reduced by acetaldehyde, while it increased their levels in detergent-soluble fractions. Pretreatment with EGF or l-glutamine prevented acetaldehyde-induced protein tyrosine phosphorylation, redistribution from intercellular junctions, and reduction in the levels of detergent-insoluble fractions of occludin, zonula occludens-1, E-cadherin, and β-catenin. These results demonstrate that acetaldehyde induces tyrosine phosphorylation and disrupts tight junction and adherens junction in human colonic mucosa, which can be prevented by EGF and glutamine.

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.

Disruption of function and localization of tight junctional structures and Mrp2 in sustained estradiol-17β-d-glucuronide-induced cholestasis

2007 ◽  
Vol 293 (1) ◽  
pp. G391-G402 ◽  
Author(s):  
Aldo D. Mottino ◽  
Tim Hoffman ◽  
Fernando A. Crocenzi ◽  
Enrique J. Sánchez Pozzi ◽  
Marcelo G. Roma ◽  
...  
Keyword(s):  
Tight Junction ◽  
Basolateral Membrane ◽  
Bile Secretion ◽  
Cholera Toxin B Subunit ◽  
Toxin B ◽  
B Subunit ◽  
Zonula Occludens ◽  
Single Bolus Dose ◽  
Zonula Occludens 1 ◽  
Estradiol 17Β

Estradiol-17β-d-glucuronide (E217G) induces immediate and profound but transient cholestasis in rats when administered as a single bolus dose. Here, we examined the consequence of sustained E217G cholestasis and assessed the function and localization of the tight junctional proteins zonula occludens-1 (ZO-1) and occludin and of the canalicular transporter multidrug resistance-associated protein-2 (Mrp2). An initial dose of E217G (15 μmol/kg iv) followed by five subsequent doses of 7.5 μmol/kg from 60 to 240 min induced a sustained 40–70% decrease in bile flow. Following their biliary retrograde administration, cholera toxin B subunit-FITC or horseradish peroxidase were detected at the sinusoidal domain, indicating opening of the paracellular route; this occurred as early as 15 min after the first dose as well as 15 min after the last dose of E217G, but not following the administration of vehicle in controls. Localization of ZO-1 and occludin was only slightly affected under acute cholestatic conditions but was severely disrupted under sustained cholestasis, with their appearance suggesting a fragmented structure. Endocytic internalization of Mrp2 to the pericanalicular region was apparent 20 min after a single E217G administration; however, Mrp2 was found more deeply internalized and partially redistributed to the basolateral membrane under sustained cholestasis. In conclusion, acute E217G-induced cholestasis increased permeability of the tight junction, while sustained cholestasis provoked a significant redistribution of ZO-1, occludin, and Mrp2 in addition to increased permeability of the tight junction. Altered tight junction integrity likely contributes to impaired bile secretion and may be causally related to changes in Mrp2 localization.

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