scholarly journals p120 Catenin Regulates Dendritic Spine and Synapse Development through Rho-Family GTPases and Cadherins

Neuron ◽  
2006 ◽  
Vol 51 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Lisa P. Elia ◽  
Miya Yamamoto ◽  
Keling Zang ◽  
Louis F. Reichardt
Keyword(s):  
Dendritic Spine ◽  
Synapse Development ◽  
P120 Catenin ◽  
Rho Family Gtpases ◽  
Rho Family

scholarly journals Dendritic spine geometry can localize GTPase signaling in neurons

2015 ◽  
Vol 26 (22) ◽  
pp. 4171-4181 ◽  
Author(s):  
Samuel A. Ramirez ◽  
Sridhar Raghavachari ◽  
Daniel J. Lew
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Primary Cilia ◽  
Reaction Diffusion ◽  
Reaction Diffusion Equations ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Sustained Activation

Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread from the stimulated spine, Cdc42 activity remains localized to the stimulated spine. Because Cdc42 itself diffuses rapidly in and out of the spine, the basis for the retention of Cdc42 activity in the stimulated spine long after synaptic stimulation has ceased is unclear. Here we model the spread of Cdc42 activation at dendritic spines by means of reaction-diffusion equations solved on spine-like geometries. Excitable behavior arising from positive feedback in Cdc42 activation leads to spreading waves of Cdc42 activity. However, because of the very narrow neck of the dendritic spine, wave propagation is halted through a phenomenon we term geometrical wave-pinning. We show that this can account for the localization of Cdc42 activity in the stimulated spine, and, of interest, retention is enhanced by high diffusivity of Cdc42. Our findings are broadly applicable to other instances of signaling in extreme geometries, including filopodia and primary cilia.

p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion

2001 ◽  
Vol 114 (4) ◽  
pp. 695-707 ◽  
Author(s):  
I. Grosheva ◽  
M. Shtutman ◽  
M. Elbaum ◽  
A.D. Bershadsky
Keyword(s):  
Cell Motility ◽  
Small Gtpases ◽  
Cell Junctions ◽  
P120 Catenin ◽  
Contact Formation ◽  
Cell Locomotion ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
E Cadherin ◽  
Cell Cell

The molecular basis for contact inhibition of cell locomotion is still largely unknown. Cadherins, the major receptors mediating cell-cell adhesion, associate in the cytoplasm with armadillo family proteins, including beta- and gamma-catenin and p120 catenin (p120ctn). E-cadherin-mediated contact formation was shown to inhibit cellular motility. We examine whether p120ctn may have a role in this regulation. We show here that overexpression of p120ctn in fibroblasts and epithelial cells induces pronounced changes in cell shape, motility and adhesion to the extracellular matrix. p120ctn-transfected cells display increased filopodial/lamellipodial activity, decreased contractility and focal adhesion formation, and augmented migratory ability. These effects of p120ctn are mediated by small GTPases of the Rho family. Direct assessment of the activity of these GTPases in cells expressing a 5-fold higher level of p120ctn as compared to non-transfected control cells revealed significant augmentation of Cdc42 and Rac activity. Moreover, co-transfection of p120ctn with dominant-negative Cdc42 and Rac, or constitutively active Rho suppressed morphological effects of p120ctn. Confocal immunofluorescence visualization of the distribution of endogenous p120ctn in dense cultures showed that formation of cadherin-mediated cell-cell contacts is accompanied by sequestering of p120ctn to the junction regions. In sparse cultures p120ctn is distributed over the cytoplasm. Co-transfection with an excess of E-cadherin leads to sequestration of exogenous p120ctn to cell-cell junctions or to small cadherin-containing vesicles, and abolishes p120ctn effects on cell morphology. Thus, p120ctn may couple the formation and disruption of cadherin-mediated contacts with regulation of cell motility by triggering pathway(s) affecting Rho family GTPases.

scholarly journals P120 Catenin Regulates the Actin Cytoskeleton via Rho Family Gtpases

2000 ◽  
Vol 150 (3) ◽  
pp. 567-580 ◽  
Author(s):  
Nicole K. Noren ◽  
Betty P. Liu ◽  
Keith Burridge ◽  
Bertolt Kreft
Keyword(s):  
Focal Adhesions ◽  
Dendritic Morphology ◽  
Dominant Negative ◽  
Cell Junctions ◽  
P120 Catenin ◽  
Rhoa Activity ◽  
Juxtamembrane Region ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
Cell Cell

Cadherins are calcium-dependent adhesion molecules responsible for the establishment of tight cell–cell contacts. p120 catenin (p120ctn) binds to the cytoplasmic domain of cadherins in the juxtamembrane region, which has been implicated in regulating cell motility. It has previously been shown that overexpression of p120ctn induces a dendritic morphology in fibroblasts (Reynolds, A.B., J. Daniel, Y. Mo, J. Wu, and Z. Zhang. 1996. Exp. Cell Res. 225:328–337.). We show here that this phenotype is suppressed by coexpression of cadherin constructs that contain the juxtamembrane region, but not by constructs lacking this domain. Overexpression of p120ctn disrupts stress fibers and focal adhesions and results in a decrease in RhoA activity. The p120ctn-induced phenotype is blocked by dominant negative Cdc42 and Rac1 and by constitutively active Rho-kinase, but is enhanced by dominant negative RhoA. p120ctn overexpression increased the activity of endogenous Cdc42 and Rac1. Exploring how p120ctn may regulate Rho family GTPases, we find that p120ctn binds the Rho family exchange factor Vav2. The behavior of p120ctn suggests that it is a vehicle for cross-talk between cell–cell junctions and the motile machinery of cells. We propose a model in which p120ctn can shuttle between a cadherin-bound state and a cytoplasmic pool in which it can interact with regulators of Rho family GTPases. Factors that perturb cell–cell junctions, such that the cytoplasmic pool of p120ctn is increased, are predicted to decrease RhoA activity but to elevate active Rac1 and Cdc42, thereby promoting cell migration.

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

scholarly journals Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells

2015 ◽  
Vol 26 (22) ◽  
pp. 4163-4170 ◽  
Author(s):  
Sam Cooper ◽  
Amine Sadok ◽  
Vicky Bousgouni ◽  
Chris Bakal
Keyword(s):  
Quantitative Imaging ◽  
Three Dimensional ◽  
Shape Space ◽  
Melanoma Cells ◽  
Collagen Matrices ◽  
Morphological Heterogeneity ◽  
Rho Family Gtpases ◽  
Metastatic Process ◽  
Rho Family ◽  
Single Living

Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space—an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively.

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