scholarly journals Telophase correction refines division orientation in stratified epithelia

2019 ◽  
Author(s):  
Kendall J. Lough ◽  
Kevin M. Byrd ◽  
Carlos P. Descovich ◽  
Danielle C. Spitzer ◽  
Abby J. Bergman ◽  
...  
Keyword(s):  
Adherens Junction ◽  
Scaffolding Protein ◽  
Spindle Positioning ◽  
Precise Control ◽  
Extrinsic Cues ◽  
Spindle Rotation ◽  
Proliferation And Differentiation ◽  
Local Cell ◽  
Division Axis ◽  
Adherens Junction Proteins

ABSTRACTDuring organogenesis, precise control of spindle orientation ensures a proper balance of proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events that occur early in mitosis. Here, we identify a previously uncharacterized orientation mechanism that occurs during telophase, correcting erroneous oblique orientations that unexpectedly persist into anaphase. The directionality of reorientation—towards either planar or perpendicular—correlates with the maintenance or loss of basal contact by the apical daughter. While the conserved scaffolding protein Pins/LGN is believed to function primarily through initial spindle positioning, we now show it also functions actively during telophase to reorient oblique divisions toward perpendicular. The ability to undergo telophase correction is also critically dependent upon an LGN-independent pathway involving the tension-sensitive adherens junction proteins vinculin, a-catenin and afadin, and correction directionality is influenced by local cell density. Failure of this reorientation mechanism impacts tissue architecture, as excessive oblique divisions induce precocious differentiation. The division orientation plasticity provided by telophase correction may provide a means for progenitors to dynamically respond to extrinsic cues provided by neighboring cells in order to adapt to local tissue needs.

scholarly journals Telophase correction refines division orientation in stratified epithelia

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kendall J Lough ◽  
Kevin M Byrd ◽  
Carlos P Descovich ◽  
Danielle C Spitzer ◽  
Abby J Bergman ◽  
...  
Keyword(s):  
Adherens Junction ◽  
Scaffolding Protein ◽  
Spindle Positioning ◽  
Precise Control ◽  
Spindle Rotation ◽  
Proliferation And Differentiation ◽  
Orientation Mechanism ◽  
Division Axis ◽  
Adherens Junction Proteins ◽  
Junction Proteins

During organogenesis, precise control of spindle orientation balances proliferation and differentiation. In the developing murine epidermis, planar and perpendicular divisions yield symmetric and asymmetric fate outcomes, respectively. Classically, division axis specification involves centrosome migration and spindle rotation, events occurring early in mitosis. Here, we identify a novel orientation mechanism which corrects erroneous anaphase orientations during telophase. The directionality of reorientation correlates with the maintenance or loss of basal contact by the apical daughter. While the scaffolding protein LGN is known to determine initial spindle positioning, we show that LGN also functions during telophase to reorient oblique divisions toward perpendicular. The fidelity of telophase correction also relies on the tension-sensitive adherens junction proteins vinculin, α-E-catenin, and afadin. Failure of this corrective mechanism impacts tissue architecture, as persistent oblique divisions induce precocious, sustained differentiation. The division orientation plasticity provided by telophase correction may enable progenitors to adapt to local tissue needs.

Gα12 regulates epithelial cell junctions through Src tyrosine kinases

2003 ◽  
Vol 285 (5) ◽  
pp. C1281-C1293 ◽  
Author(s):  
Tobias N. Meyer ◽  
Jennifer Hunt ◽  
Catherine Schwesinger ◽  
Bradley M. Denker
Keyword(s):  
Epithelial Cell ◽  
Tyrosine Kinase ◽  
Mdck Cells ◽  
Adherens Junction ◽  
Paracellular Permeability ◽  
Cell Junctions ◽  
Scaffolding Protein ◽  
Junctional Complex ◽  
Adherens Junction Proteins ◽  
Junction Proteins

Regulation and assembly of the epithelial cell junctional complex involve multiple signaling mechanisms, including heterotrimeric G proteins. Recently, we demonstrated that Gα12 binds to the tight junction scaffolding protein ZO-1 through the SH3 domain and that activated Gα12 increases paracellular permeability in Madin-Darby canine kidney (MDCK) cells (Meyer et al. J Biol Chem 277: 24855-24858, 2002). In the present studies, we explore the effects of Gα12 expression on tight and adherens junction proteins and examine downstream signaling pathways. By confocal microscopy, we detect disrupted tight and adherens junction proteins with increased actin stress fibers in constitutively active Gα12 (QLα12)-expressing MDCK cells. The normal distribution of ZO-1 and Na-K-ATPase was altered in QLα12-expressing MDCK cells, consistent with loss of polarity. We found that the tyrosine kinase inhibitor genistein and the Src-specific inhibitor PP-2 reversibly abrogated the QLα12 phenotype on the junctional complex. Junctional protein localization was preserved in PP-2- or genistein-treated QLα12-expressing cells, and the increase in paracellular permeability as measured by transepithelial resistance and [3H]mannitol flux was prevented by the inhibitors. Src activity was increased in QLα12-expressing MDCK cells as assessed by Src autophosphorylation, and β-catenin tyrosine phosphorylation was also increased, although there was no detectable increase in Rho activity. Taken together, these results indicate that Gα12 regulates MDCK cell junctions, in part through Src tyrosine kinase pathways.

scholarly journals Tight Junctions in Cell Proliferation

2019 ◽  
Vol 20 (23) ◽  
pp. 5972 ◽  
Author(s):  
Mónica Díaz-Coránguez ◽  
Xuwen Liu ◽  
David A. Antonetti
Keyword(s):  
Cell Proliferation ◽  
Adherens Junction ◽  
Barrier Properties ◽  
Endothelial Cell Proliferation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Associated Proteins ◽  
Barrier Regulation ◽  
Adherens Junction Proteins

Tight junction (TJ) proteins form a continuous intercellular network creating a barrier with selective regulation of water, ion, and solutes across endothelial, epithelial, and glial tissues. TJ proteins include the claudin family that confers barrier properties, members of the MARVEL family that contribute to barrier regulation, and JAM molecules, which regulate junction organization and diapedesis. In addition, the membrane-associated proteins such as MAGUK family members, i.e., zonula occludens, form the scaffold linking the transmembrane proteins to both cell signaling molecules and the cytoskeleton. Most studies of TJ have focused on the contribution to cell-cell adhesion and tissue barrier properties. However, recent studies reveal that, similar to adherens junction proteins, TJ proteins contribute to the control of cell proliferation. In this review, we will summarize and discuss the specific role of TJ proteins in the control of epithelial and endothelial cell proliferation. In some cases, the TJ proteins act as a reservoir of critical cell cycle modulators, by binding and regulating their nuclear access, while in other cases, junctional proteins are located at cellular organelles, regulating transcription and proliferation. Collectively, these studies reveal that TJ proteins contribute to the control of cell proliferation and differentiation required for forming and maintaining a tissue barrier.

scholarly journals Drosophila p120catenin plays a supporting role in cell adhesion but is not an essential adherens junction component

2003 ◽  
Vol 160 (3) ◽  
pp. 433-449 ◽  
Author(s):  
Steven H. Myster ◽  
Robert Cavallo ◽  
Charles T. Anderson ◽  
Donald T. Fox ◽  
Mark Peifer
Keyword(s):  
Cell Adhesion ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Null Alleles ◽  
Juxtamembrane Region ◽  
Genes Encoding ◽  
Positive Modulator ◽  
Adherens Junction Proteins ◽  
Junction Structure ◽  
Junction Proteins

Cadherin–catenin complexes, localized to adherens junctions, are essential for cell–cell adhesion. One means of regulating adhesion is through the juxtamembrane domain of the cadherin cytoplasmic tail. This region is the binding site for p120, leading to the hypothesis that p120 is a key regulator of cell adhesion. p120 has also been suggested to regulate the GTPase Rho and to regulate transcription via its binding partner Kaiso. To test these hypothesized functions, we turned to Drosophila, which has only a single p120 family member. It localizes to adherens junctions and binds the juxtamembrane region of DE-cadherin (DE-cad). We generated null alleles of p120 and found that mutants are viable and fertile and have no substantial changes in junction structure or function. However, p120 mutations strongly enhance mutations in the genes encoding DE-cadherin or Armadillo, the β-catenin homologue. Finally, we examined the localization of p120 during embryogenesis. p120 localizes to adherens junctions, but its localization there is less universal than that of core adherens junction proteins. Together, these data suggest that p120 is an important positive modulator of adhesion but that it is not an essential core component of adherens junctions.

Ectopic expression of gastrokine 1 in gastric cancer cells up-regulates tight and adherens junction proteins network

2015 ◽  
Vol 211 (8) ◽  
pp. 577-583 ◽  
Author(s):  
Emilia Rippa ◽  
Filomena Altieri ◽  
Chiara Stella Di Stadio ◽  
Giuseppina Miselli ◽  
Annalisa Lamberti ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Adherens Junction ◽  
Gastric Cancer Cells ◽  
Gastrokine 1 ◽  
Adherens Junction Proteins ◽  
Junction Proteins

scholarly journals UNC-2 CaV2 channel localization at presynaptic active zones depends on UNC-10/RIM and SYD-2/Liprin-α in Caenorhabditis elegans

2021 ◽  
Author(s):  
Kelly H. Oh ◽  
Mia Krout ◽  
Janet E. Richmond ◽  
Hongkyun Kim
Keyword(s):  
Active Zone ◽  
Calcium Influx ◽  
Genetic Screen ◽  
Scaffolding Protein ◽  
Tight Coupling ◽  
Forward Genetic Screen ◽  
Precise Control ◽  
C Elegans ◽  
Vesicle Exocytosis ◽  
Active Zones

AbstractPresynaptic active zone proteins couple calcium influx with synaptic vesicle exocytosis. However, the control of presynaptic calcium channel clustering by active zone proteins is not completely understood. In a C. elegans forward genetic screen, we find that UNC-10/RIM (Rab3-interacting molecule) and SYD-2/Liprin-α regulate presynaptic clustering of UNC-2, the CaV2 channel ortholog. We further quantitatively analyzed live animals using endogenously GFP-tagged UNC-2 and active zone components. Consistent with the interaction between RIM and CaV2 in mammals, the intensity and number of UNC-2 channel clusters at presynaptic terminals were greatly reduced in unc-10 mutant animals. To understand how SYD-2 regulates presynaptic UNC-2 channel clustering, we analyzed presynaptic localization of endogenous SYD-2, UNC-10, RIMB-1/RIM-BP (RIM binding protein), and ELKS-1. Our analysis revealed that while SYD-2 is the most critical for active zone assembly, loss of SYD-2 function does not completely abolish presynaptic localization of UNC-10, RIMB-1, and ELKS-1, suggesting an existence of SYD-2-independent active zone assembly. UNC-2 localization analysis in double and triple mutants of active zone components show that SYD-2 promotes UNC-2 clustering by partially controlling UNC-10 localization, and ELKS-1 and RIMB-1 also contribute to UNC-2 channel clustering. In addition, we find that core active zone proteins are unequal in their abundance. While the abundance of UNC-10 at the active zone is comparable to UNC-2, SYD-2 and ELKS-1 are twice more and RIMB-1 four times more abundant than UNC-2. Together our data show that UNC-10, SYD-2, RIMB-1, and ELKS-1 control presynaptic UNC-2 channel clustering in redundant yet distinct manners.Significance StatementPrecise control of neurotransmission is dependent on the tight coupling of the calcium influx through voltage-gated calcium channels (VGCCs) to the exocytosis machinery at the presynaptic active zones. However, how these VGCCs are tethered to the active zone is incompletely understood. To understand the mechanism of presynaptic VGCC localization, we performed a C. elegans forward genetic screen and quantitatively analyzed endogenous active zones and presynaptic VGCCs. In addition to RIM (Rab3-interacting molecule), our study finds that SYD-2/Liprin-α is critical for presynaptic localization of VGCCs. Yet, the loss of SYD-2, the master active zone scaffolding protein, does not completely abolish the presynaptic localization of the VGCC, showing that the active zone is a resilient structure assembled by redundant mechanisms.

Altered expression and interaction of adherens junction proteins in the developing OLM of the Rho(−/−) mouse

2007 ◽  
Vol 85 (5) ◽  
pp. 714-720 ◽  
Author(s):  
Matthew Campbell ◽  
Marian Humphries ◽  
Paul Kenna ◽  
Peter Humphries ◽  
Brenda Brankin
Keyword(s):  
Adherens Junction ◽  
Altered Expression ◽  
Adherens Junction Proteins ◽  
Junction Proteins

scholarly journals Cooked Red Lentils Dose-Dependently Modulate the Colonic Microenvironment in Healthy C57Bl/6 Male Mice

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1853 ◽  
Author(s):  
Daniela Graf ◽  
Jennifer M. Monk ◽  
Dion Lepp ◽  
Wenqing Wu ◽  
Laurel McGillis ◽  
...  
Keyword(s):  
Adherens Junction ◽  
Basal Diet ◽  
Fecal Microbiota ◽  
Male Mice ◽  
Soluble Fiber ◽  
Intestinal Health ◽  
Α Diversity ◽  
Health Promoting ◽  
And Function ◽  
Adherens Junction Proteins

Dietary pulses, including lentils, are protein-rich plant foods that are enriched in intestinal health-promoting bioactives, such as non-digestible carbohydrates and phenolic compounds. The aim of this study was to investigate the effect of diets supplemented with cooked red lentils on the colonic microenvironment (microbiota composition and activity and epithelial barrier integrity and function). C57Bl/6 male mice were fed one of five diets: a control basal diet (BD), a BD-supplemented diet with 5, 10 or 20% cooked red lentils (by weight), or a BD-supplemented diet with 0.7% pectin (equivalent soluble fiber level as found in the 20% lentil diet). Red lentil supplementation resulted in increased: (1) fecal microbiota α-diversity; (2) abundance of short-chain fatty acid (SCFA)-producing bacteria (e.g., Prevotella, Roseburia and Dorea spp.); (3) concentrations of fecal SCFAs; (4) mRNA expression of SCFA receptors (G-protein-coupled receptors (GPR 41 and 43) and tight/adherens junction proteins (Zona Occulden-1 (ZO-1), Claudin-2, E-cadherin). Overall, 20% lentil had the greatest impact on colon health outcomes, which were in part explained by a change in the soluble and insoluble fiber profile of the diet. These results support recent public health recommendations to increase consumption of plant-based protein foods for improved health, in particular intestinal health.

scholarly journals Regulation of Adherens Junction Dynamics by Phosphorylation Switches

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Cristina Bertocchi ◽  
Megha Vaman Rao ◽  
Ronen Zaidel-Bar
Keyword(s):  
Actin Cytoskeleton ◽  
Enzymatic Activity ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Adaptor Proteins ◽  
Cell Junction ◽  
Internal Forces ◽  
Adherens Junction Proteins ◽  
Junction Proteins

Adherens junctions connect the actin cytoskeleton of neighboring cells through transmembrane cadherin receptors and a network of adaptor proteins. The interactions between these adaptors and cadherin as well as the activity of actin regulators localized to adherens junctions are tightly controlled to facilitate cell junction assembly or disassembly in response to changes in external or internal forces and/or signaling. Phosphorylation of tyrosine, serine, or threonine residues acts as a switch on the majority of adherens junction proteins, turning “on” or “off” their interactions with other proteins and/or their enzymatic activity. Here, we provide an overview of the kinases and phosphatases regulating phosphorylation of adherens junction proteins and bring examples of phosphorylation events leading to the assembly or disassembly of adherens junctions, highlighting the important role of phosphorylation switches in regulating their dynamics.

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