scholarly journals Association of Rho-associated protein kinase 1 with E-cadherin complexes is mediated by p120-catenin

2012 ◽  
Vol 23 (1) ◽  
pp. 99-110 ◽  
Author(s):  
Andrew L. Smith ◽  
Michael R. Dohn ◽  
Meredith V. Brown ◽  
Albert B. Reynolds
Keyword(s):  
Protein Kinase ◽  
Rho Gtpase ◽  
Actin Dynamics ◽  
Physical Interaction ◽  
P120 Catenin ◽  
Proteomic Approach ◽  
Downstream Effectors ◽  
Blocking Antibodies ◽  
The Relationship ◽  
E Cadherin

The dynamic functional linkage of cadherins with the underlying actin cytoskeleton is tightly regulated to achieve proper cell–cell adhesion. p120-catenin (p120) regulates both cadherin stability and actin dynamics, but the relationship between these two functions remains unclear. Using a novel proteomic approach called reversible cross-link immunoprecipitation, or ReCLIP, we previously identified a physical interaction between p120 and Rho-associated protein kinase 1 (ROCK1), a major effector of RhoA. In this paper, we show that a discrete fraction of cellular ROCK1 coimmunoprecipitates with p120 and precisely colocalizes to adherens junctions (AJs). Manipulation of AJs using a calcium-switch assay and cadherin-blocking antibodies indicates direct recruitment of ROCK1 to newly forming junctions. Importantly, we find that p120 links ROCK1 to the cadherin complex, as ROCK1 coimmunoprecipitates with wild-type but not p120-uncoupled E-cadherin. Moreover, depletion of ROCK1 using short-hairpin RNA results in dramatic mislocalization of the cadherin complex and junctional actin. These data are consistent with a model in which p120 dynamically regulates Rho-GTPase activity at the cadherin complex through transient interaction with several of its up- and downstream effectors, including ROCK1.

scholarly journals p120-Catenin Inhibits VE-Cadherin Internalization through a Rho-independent Mechanism

2009 ◽  
Vol 20 (7) ◽  
pp. 1970-1980 ◽  
Author(s):  
Christine M. Chiasson ◽  
Kristin B. Wittich ◽  
Peter A. Vincent ◽  
Victor Faundez ◽  
Andrew P. Kowalczyk
Keyword(s):  
Plasma Membrane ◽  
Rho Gtpase ◽  
Retention Mechanism ◽  
Endocytic Pathway ◽  
Membrane Domains ◽  
P120 Catenin ◽  
Rhoa Activity ◽  
Endocytic Machinery ◽  
Endocytic Compartments ◽  
The Relationship

p120-catenin is a cytoplasmic binding partner of cadherins and functions as a set point for cadherin expression by preventing cadherin endocytosis, and degradation. p120 is known to regulate cell motility and invasiveness by inhibiting RhoA activity. However, the relationship between these functions of p120 is not understood. Here, we provide evidence that p120 functions as part of a plasma membrane retention mechanism for VE-cadherin by preventing the recruitment of VE-cadherin into membrane domains enriched in components of the endocytic machinery, including clathrin and the adaptor complex AP-2. The mechanism by which p120 regulates VE-cadherin entry into endocytic compartments is dependent on p120's interaction with the cadherin juxtamembrane domain, but occurs independently of p120's prevention of Rho GTPase activity. These findings clarify the mechanism for p120's function in stabilizing VE-cadherin at the plasma membrane and demonstrate a novel role for p120 in modulating the availability of cadherins for entry into a clathrin-dependent endocytic pathway.

scholarly journals E-cadherin endocytosis is modulated by p120-catenin through the opposing actions of RhoA and Arf1

2018 ◽  
Author(s):  
Joshua Greig ◽  
Natalia A. Bulgakova
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Actin Dynamics ◽  
P120 Catenin ◽  
Vital Importance ◽  
C Terminus ◽  
Opposing Effects ◽  
Actin Remodelling ◽  
Tissue Tension ◽  
E Cadherin

AbstractThe regulation of E-cadherin at the plasma membrane by endocytosis is of vital importance for developmental and disease. p120-catenin, which binds to the E-cadherin C-terminus, can both promote and inhibit E-cadherin endocytosis. However, little is known about what determines the directionality of p120-catenin activity, and the molecules downstream. Here, we have discovered that p120-catenin fine-tunes the clathrin-mediated endocytosis of E-cadherin in Drosophila embryonic epidermal cells. It simultaneously activated two actin-remodelling pathways with opposing effects: RhoA, which stabilized E-cadherin at the membrane, and Arf1, which promoted internalization. Epistasis experiments revealed that RhoA additionally inhibited Arf1. E-cadherin was efficiently endocytosed only in the presence of intermediate p120-catenin amounts with too little and too much p120-catenin inhibiting E-cadherin endocytosis. Finally, we found that p120-catenin levels altered the tension of the plasma membrane. Altogether, this shows that p120-catenin is a central hub which co-ordinates cell adhesion, endocytosis, and actin dynamics with tissue tension.

scholarly journals Intestinal HT-29 cells with dysfunction of E-cadherin show increased pp60src activity and tyrosine phosphorylation of p120-catenin

1996 ◽  
Vol 317 (1) ◽  
pp. 279-284 ◽  
Author(s):  
Anouchka SKOUDY ◽  
Maria del Mont LLOSAS ◽  
Antonio GARCÍA de HERREROS
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
The Other ◽  
P120 Catenin ◽  
Cell Contacts ◽  
Herbimycin A ◽  
Kinase C ◽  
Ht 29 ◽  
E Cadherin

1. HT-29 M6 cells are a subpopulation of HT-29 cells that, contrarily to the parental cells, establish tight cell contacts and differentiate. Cell-to-cell contacts in HT-29 M6 cells are also regulated by protein kinase C; addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA) decreases the homotypic contacts of these cells. We show here that HT-29 cells or HT-29 M6 cells treated with PMA contain lower levels of functional E-cadherin, determined by analysing the association of this protein with the cytoskeleton. No significant differences in the localization of α-, β-, or p120-catenins were detected under the three different conditions. 2. Dysfunction of E-cadherin can be reversed by incubation of HT-29 cells with the tyrosine kinase inhibitor herbimycin A. On the other hand an augmentation of c-src activity in HT-29 cells or HT-29 M6 cells treated with PMA was observed with respect to control HT-29 M6 cells. The phosphorylation status of catenins was also investigated; in HT-29 or in HT-29 M6 cells treated with PMA, dysfunction of E-cadherin was accompanied by an increased phosphorylation of p120-catenin and by an elevated association of this protein to E-cadherin. These results suggest a role for pp60src and the pp60src substrate p120-catenin in the control of E-cadherin function in HT-29 cells.

MiR-125a-5p Alleviates Dysfunction and Inflammation of Pentylenetetrazol- induced Epilepsy Through Targeting Calmodulin-dependent Protein Kinase IV (CAMK4)

2019 ◽  
Vol 16 (4) ◽  
pp. 365-372 ◽  
Author(s):  
Qishuai Liu ◽  
Li Wang ◽  
Guizhen Yan ◽  
Weifa Zhang ◽  
Zhigang Huan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Target Gene ◽  
Luciferase Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Dependent Protein Kinase ◽  
Expression Levels ◽  
Dependent Protein ◽  
Polymerase Chain ◽  
The Relationship

Background: MicroRNAs (miRNA) are known to play a key role in the etiology and treatment of epilepsy through controlling the expression of gene. However, miR-125a-5p in the epilepsy is little known. Epilepsy in rat models was induced by Pentylenetetrazol (PTZ) and miR- 125a-5p profiles in the hippocampus were investigated in our experiment. Also, the relationship between miR-125a-5p and calmodulin-dependent protein kinase IV (CAMK4) was identified and the related mechanism was also illustrated. Methods: The miR-125a-5p mRNA expression levels were evaluated by quantitative real time polymerase chain reaction (qRT-PCR). Western Blot (WB) was used to analyze the CAMK4 protein expression levels. Seizure score, latency and duration were determined based on a Racine scale. The enzyme-linked immunosorbent assay (ELISA) was used to analyze the inflammatory factor expression. The relationship between miR-125a-5p and CAMK4 was detected through dual luciferase assay. Results: Downregulation of miR-125a-5p was observed in the hippocampus of PTZ-induced epilepsy rats. The overexpression of miR-125a-5p attenuated seizure and decreased inflammatory factor level in the hippocampus of PTZ-induced rats. The miR-125a-5p alleviated epileptic seizure and inflammation in PTZ-induced rats by suppressing its target gene, CAMK4. Conclusion: miR-125a-5p may represent a novel therapeutic treatment for PTZ-induced epilepsy by preventing the activation of CAMK4.

P120 catenin potentiates constitutive E-cadherin dimerization at the plasma membrane and regulates trans binding

2021 ◽  
Author(s):  
Vinh Vu ◽  
Taylor Light ◽  
Brendan Sullivan ◽  
Diana Greiner ◽  
Kalina Hristova ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
P120 Catenin ◽  
E Cadherin
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