scholarly journals Proteasome-mediated Degradation of Rac1-GTP during Epithelial Cell Scattering

2006 ◽  
Vol 17 (5) ◽  
pp. 2236-2242 ◽  
Author(s):  
Emma A. Lynch ◽  
Jennifer Stall ◽  
Gudila Schmidt ◽  
Philippe Chavrier ◽  
Crislyn D'Souza-Schorey
Keyword(s):  
Epithelial Cell ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Cell Contacts ◽  
Rho Family Gtpases ◽  
Cell Scattering ◽  
Rho Family ◽  
Powerful Mechanism ◽  
Sustained Activation ◽  
Cell Cell

Epithelial cells disassemble their adherens junctions and “scatter” during processes such as tumor cell invasion as well as some stages of embryonic development. Control of actin polymerization is a powerful mechanism for regulating the strength of cell–cell adhesion. In this regard, studies have shown that sustained activation of Rac1, a well-known regulator of actin dynamics, results in the accumulation of polymerized actin at cell–cell contacts in epithelia and an increase in E-cadherin–mediated adhesion. Here we show that active Rac1 is ubiquitinated and subject to proteasome-mediated degradation during the early stages of epithelial cell scattering. These findings delineate a mechanism for the down-regulation of Rac1 in the disassembly of epithelial cell–cell contacts and support the emerging theme that UPS-mediated degradation of the Rho family GTPases may serve as an efficient mechanism for GTPase deactivation in the sustained presence of Dbl-exchange factors.

scholarly journals A molecular mechanism directly linking E-cadherin adhesion to initiation of epithelial cell surface polarity

2007 ◽  
Vol 178 (2) ◽  
pp. 323-335 ◽  
Author(s):  
Lene N. Nejsum ◽  
W. James Nelson
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Cell Surface ◽  
Basolateral Membrane ◽  
Surface Polarity ◽  
Cell Contacts ◽  
Protein Receptors ◽  
Epithelial Cell Surface ◽  
E Cadherin ◽  
Cell Cell

Mechanisms involved in maintaining plasma membrane domains in fully polarized epithelial cells are known, but when and how directed protein sorting and trafficking occur to initiate cell surface polarity are not. We tested whether establishment of the basolateral membrane domain and E-cadherin–mediated epithelial cell–cell adhesion are mechanistically linked. We show that the basolateral membrane aquaporin (AQP)-3, but not the equivalent apical membrane AQP5, is delivered in post-Golgi structures directly to forming cell–cell contacts where it co-accumulates precisely with E-cadherin. Functional disruption of individual components of a putative lateral targeting patch (e.g., microtubules, the exocyst, and soluble N-ethylmaleimide–sensitive factor attachment protein receptors) did not inhibit cell–cell adhesion or colocalization of the other components with E-cadherin, but each blocked AQP3 delivery to forming cell–cell contacts. Thus, components of the lateral targeting patch localize independently of each other to cell–cell contacts but collectively function as a holocomplex to specify basolateral vesicle delivery to nascent cell–cell contacts and immediately initiate cell surface polarity.

scholarly journals Polymerase-δ-interacting protein 2 activates the RhoGEF epithelial cell transforming sequence 2 in vascular smooth muscle cells

2019 ◽  
Vol 316 (5) ◽  
pp. C621-C631 ◽  
Author(s):  
Lauren Parker Huff ◽  
Daniel Seicho Kikuchi ◽  
Elizabeth Faidley ◽  
Steven J. Forrester ◽  
Michelle Z. Tsai ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Smooth Muscle ◽  
Epithelial Cell ◽  
Vascular Smooth Muscle ◽  
Vascular Smooth Muscle Cells ◽  
Oxygen Species ◽  
Interacting Protein ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Cell Transforming

Polymerase-δ-interacting protein 2 (Poldip2) controls a wide variety of cellular functions and vascular pathologies. To mediate these effects, Poldip2 interacts with numerous proteins and generates reactive oxygen species via the enzyme NADPH oxidase 4 (Nox4). We have previously shown that Poldip2 can activate the Rho family GTPase RhoA, another signaling node within the cell. In this study, we aimed to better understand how Poldip2 activates Rho family GTPases and the functions of the involved proteins in vascular smooth muscle cells (VSMCs). RhoA is activated by guanine nucleotide exchange factors. Using nucleotide-free RhoA (isolated from bacteria) to pulldown active RhoGEFs, we found that the RhoGEF epithelial cell transforming sequence 2 (Ect2) is activated by Poldip2. Ect2 is a critical RhoGEF for Poldip2-mediated RhoA activation, because siRNA against Ect2 prevented Poldip2-mediated RhoA activity (measured by rhotekin pulldowns). Surprisingly, we were unable to detect a direct interaction between Poldip2 and Ect2, as they did not coimmunoprecipitate. Nox4 is not required for Poldip2-driven Ect2 activation, as Poldip2 overexpression induced Ect2 activation in Nox4 knockout VSMCs similar to wild-type cells. However, antioxidant treatment blocked Poldip2-induced Ect2 activation. This indicates a novel reactive oxygen species-driven mechanism by which Poldip2 regulates Rho family GTPases. Finally, we examined the function of these proteins in VSMCs, using siRNA against Poldip2 or Ect2 and determined that Poldip2 and Ect2 are both essential for vascular smooth muscle cell cytokinesis and proliferation.

Rho family GTPases are activated during HGF-stimulated prostate cancer-cell scattering

2005 ◽  
Vol 62 (3) ◽  
pp. 180-194 ◽  
Author(s):  
C. M. Wells ◽  
T. Ahmed ◽  
J. R. W. Masters ◽  
G. E. Jones
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Rho Family Gtpases ◽  
Cell Scattering ◽  
Rho Family

scholarly journals Anchorage of Microtubule Minus Ends to Adherens Junctions Regulates Epithelial Cell-Cell Contacts

Cell ◽  
2008 ◽  
Vol 135 (5) ◽  
pp. 948-959 ◽  
Author(s):  
Wenxiang Meng ◽  
Yoshimi Mushika ◽  
Tetsuo Ichii ◽  
Masatoshi Takeichi
Keyword(s):  
Epithelial Cell ◽  
Adherens Junctions ◽  
Cell Contacts ◽  
Cell Cell

scholarly journals The interplay of cell–cell and cell–substrate adhesion in collective cell migration

2014 ◽  
Vol 11 (100) ◽  
pp. 20140684 ◽  
Author(s):  
Chenlu Wang ◽  
Sagar Chowdhury ◽  
Meghan Driscoll ◽  
Carole A. Parent ◽  
S. K. Gupta ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Actin Polymerization ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Shapes ◽  
Cell Substrate Adhesion ◽  
Cell Cell

Collective cell migration often involves notable cell–cell and cell–substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell–substrate adhesion and cell–cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells ( Dictyostelium discoideum ), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell–cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell–cell contacts. To further investigate cell–cell/cell–substrate interactions, we used optical micromanipulation to form cell–substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell–substrate contact.

Regulating actin dynamics in neuronal growth cones by ADF/cofilin and Rho family GTPases

2000 ◽  
Vol 44 (2) ◽  
pp. 126-144 ◽  
Author(s):  
Thomas B. Kuhn ◽  
Peter J. Meberg ◽  
Michael D. Brown ◽  
Barbara W. Bernstein ◽  
Laurie S. Minamide ◽  
...  
Keyword(s):  
Growth Cones ◽  
Actin Dynamics ◽  
Neuronal Growth ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Neuronal Growth Cones

scholarly journals Regulation of Rho Family GTPases by Cell-Cell and Cell-Matrix Adhesion

2002 ◽  
Vol 35 (2) ◽  
Author(s):  
WILLIAM T. ARTHUR ◽  
NICOLE K. NOREN ◽  
KEITH BURRIDGE
Keyword(s):  
Matrix Adhesion ◽  
Cell Matrix ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Cell Matrix Adhesion ◽  
Cell Cell
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