scholarly journals A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence in Caenorhabditis elegans

Genetics ◽  
2016 ◽  
Vol 202 (3) ◽  
pp. 1153-1166 ◽  
Author(s):  
A. L. Fry ◽  
J. T. Laboy ◽  
H. Huang ◽  
A. C. Hart ◽  
K. R. Norman
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Egf Signaling

Rac is a dominant regulator of cadherin-directed actin assembly that is activated by adhesive ligation independently of Tiam1

2007 ◽  
Vol 292 (3) ◽  
pp. C1061-C1069 ◽  
Author(s):  
Astrid Kraemer ◽  
Marita Goodwin ◽  
Suzie Verma ◽  
Alpha S. Yap ◽  
Radiya G. Ali
Keyword(s):  
Signaling Pathway ◽  
Dominant Negative ◽  
Signaling Cascades ◽  
Potential Contribution ◽  
Actin Assembly ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Signaling Receptors ◽  
The Impact ◽  
E Cadherin

Classic cadherins function as adhesion-activated cell signaling receptors. On adhesive ligation, cadherins induce signaling cascades leading to actin cytoskeletal reorganization that is imperative for cadherin function. In particular, cadherin ligation activates actin assembly by the actin-related protein (Arp)2/3 complex, a process that critically affects the ability of cells to form and extend cadherin-based contacts. However, the signaling pathway(s) that activate Arp2/3 downstream of cadherin adhesion remain poorly understood. In this report we focused on the Rho family GTPases Rac and Cdc42, which can signal to Arp2/3. We found that homophilic engagement of E-cadherin simultaneously activates both Rac1 and Cdc42. However, by comparing the impact of dominant-negative Rac1 and Cdc42 mutants, we show that Rac1 is the dominant regulator of cadherin-directed actin assembly and homophilic contact formation. To pursue upstream elements of the Rac1 signaling pathway, we focused on the potential contribution of Tiam1 to cadherin-activated Rac signaling. We found that Tiam1 or the closely-related Tiam2/STEF1 was recruited to cell-cell contacts in an E-cadherin-dependent fashion. Moreover, a dominant-negative Tiam1 mutant perturbed cell spreading on cadherin-coated substrata. However, disruption of Tiam1 activity with dominant-negative mutants or RNA interference did not affect the ability of E-cadherin ligation to activate Rac1. We conclude that Rac1 critically influences cadherin-directed actin assembly as part of a signaling pathway independent of Tiam1.

Regulation of epithelial tubule formation by Rho family GTPases

2006 ◽  
Vol 290 (5) ◽  
pp. C1297-C1309 ◽  
Author(s):  
Randi Eisen ◽  
Shereaf Walid ◽  
Don R. Ratcliffe ◽  
George K. Ojakian
Keyword(s):  
Signaling Pathway ◽  
Tight Junctions ◽  
Mdck Cells ◽  
Rho Kinase ◽  
Collagen Gel ◽  
Dominant Negative ◽  
Tubule Formation ◽  
Rho Family Gtpases ◽  
Epithelial Remodeling ◽  
Rho Family

Previous work has established that the integrin signal transduction pathway plays an important role in the regulation of epithelial tubule formation. Furthermore, it has been demonstrated that Rho-kinase, an effector of the Rho signaling pathway, is an important downstream modulator of collagen-mediated renal and mammary epithelial tubule morphogenesis. In the present study, MDCK cells that expressed mutant dominant-negative, constitutively active Rho family GTPases were used to provide further insight into Rho-GTPase signaling and the regulation of epithelial tubule formation. Using collagen gel overlays on MDCK cells as a model system, we observed phosphorylated myosin light chain (pMLC) at the leading edge of migrating lamellipodia. This epithelial remodeling led to the formation of multicellular branching epithelial tubular structures with extensive tight junctions. However, in cells expressing dominant-negative RhoN19, MLC phosphorylation, epithelial remodeling, and tubule formation were inhibited. Instead, only small apical lumens with a solitary tight junctional ring were observed, providing further evidence that Rho signaling through Rho-kinase is important in the regulation of epithelial tubule formation. Because the present model for the Rho signaling pathway proposes that Rac plays a prominent but reciprocal role in cell regulation, experiments were conducted using cells that expressed constitutively active RacV12. When incubated with collagen gels, RacV12-expressing cells formed small apical lumens with simple tight junctions, suggesting that Rac1 signaling also has a prominent role in the regulation of epithelial morphogenesis. Complementary collagen gel overlay experiments with wild-type MDCK cells demonstrated that endogenous Rac1 activation levels decreased over a time course consistent with lamellipodia and tubule formation. Under these conditions, Rac1 was initially localized to the basolateral membrane. However, after epithelial remodeling, activated Rac1 was observed primarily in lamellipodia. These studies support a model in which Rac1 and RhoA are important modulators of epithelial tubule formation.

The role of Rho-family GTPases in human glioblastomas

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
S Seta ◽  
M Herr ◽  
S Horn ◽  
D Koch ◽  
T Vogt ◽  
...  
Keyword(s):  
Rho Family Gtpases ◽  
Rho Family

scholarly journals R-cadherin influences cell motility via Rho family GTPases. Vol. 279 (2004) 31041-31049

2004 ◽  
Vol 279 (42) ◽  
pp. 44229-44230
Author(s):  
Emhonta Johnson ◽  
Christopher S. Theisen ◽  
Keith R. Johnson ◽  
Margaret J. Wheelock
Keyword(s):  
Cell Motility ◽  
Rho Family Gtpases ◽  
Rho Family

scholarly journals Structure Based Drug Design in Novel Druggable Pockets on Rho Family GTPases

2012 ◽  
Vol 102 (3) ◽  
pp. 620a
Author(s):  
Juan Manuel Ortiz-Sanchez ◽  
Barry J. Grant ◽  
J. Andrew McCammon
Keyword(s):  
Drug Design ◽  
Structure Based Drug Design ◽  
Rho Family Gtpases ◽  
Rho Family
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