scholarly journals How cells determine the number of polarity sites

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jian-geng Chiou ◽  
Kyle D Moran ◽  
Daniel J Lew

The diversity of cell morphologies arises, in part, through regulation of cell polarity by Rho-family GTPases. A poorly understood but fundamental question concerns the regulatory mechanisms by which different cells generate different numbers of polarity sites. Mass-conserved activator-substrate (MCAS) models that describe polarity circuits develop multiple initial polarity sites, but then those sites engage in competition, leaving a single winner. Theoretical analyses predicted that competition would slow dramatically as GTPase concentrations at different polarity sites increase towards a 'saturation point', allowing polarity sites to coexist. Here, we test this prediction using budding yeast cells, and confirm that increasing the amount of key polarity proteins results in multiple polarity sites and simultaneous budding. Further, we elucidate a novel design principle whereby cells can switch from competition to equalization among polarity sites. These findings provide insight into how cells with diverse morphologies may determine the number of polarity sites.

Author(s):  
Jian-geng Chiou ◽  
Kyle D. Moran ◽  
Daniel J. Lew

AbstractThe diversity of cell morphologies arises, in part, through regulation of cell polarity by Rho-family GTPases. A poorly understood but fundamental question concerns the regulatory mechanisms by which different cells can generate different numbers of polarity sites. Theoretical models of polarity circuits develop multiple initial polarity sites, but then those sites engage in competition, leaving a single winner. The timescale of competition slows dramatically as GTPase concentrations at polarity sites approach a “saturation point”, allowing multiple sites to coexist. Here, we show that these principles hold in more complex mechanistic models of the Saccharomyces cerevisiae polarity machinery, and confirm model predictions in vivo. Further, we elucidate a novel design principle whereby cells can switch from competition to equalization among polarity sites. These findings provide insight into how cells determine the number of polarity sites.


Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2279
Author(s):  
Silvestar Beljan ◽  
Maja Herak Bosnar ◽  
Helena Ćetković

Non-bilaterian animals consist of four phyla; Porifera, Cnidaria, Ctenophora, and Placozoa. These early-diverging animals are crucial for understanding the evolution of the entire animal lineage. The Rho family of proteins make up a major branch of the Ras superfamily of small GTPases, which function as key molecular switches that play important roles in converting and amplifying external signals into cellular responses. This review represents a compilation of the current knowledge on Rho-family GTPases in non-bilaterian animals, the available experimental data about their biochemical characteristics and functions, as well as original bioinformatics analysis, in order to gain a general insight into the evolutionary history of Rho-family GTPases in simple animals.


2019 ◽  
Vol 22 (1) ◽  
pp. 120-134 ◽  
Author(s):  
Halil Bagci ◽  
Neera Sriskandarajah ◽  
Amélie Robert ◽  
Jonathan Boulais ◽  
Islam E. Elkholi ◽  
...  

2014 ◽  
Vol 25 (13) ◽  
pp. 1995-2005 ◽  
Author(s):  
Laurent Guillemot ◽  
Diego Guerrera ◽  
Domenica Spadaro ◽  
Rocio Tapia ◽  
Lionel Jond ◽  
...  

The regulation of Rho-family GTPases is crucial to direct the formation of cell–cell junctions and tissue barriers. Cingulin (CGN) and paracingulin (CGNL1) control RhoA activation in epithelial cells by interacting with RhoA guanidine exchange factors. CGNL1 depletion also inhibits Rac1 activation during junction assembly. Here we show that, unexpectedly, Madin–Darby canine kidney epithelial cells depleted of both CGN and CGNL1 (double-KD cells) display normal Rac1 activation and tight junction (TJ) formation, despite decreased junctional recruitment of the Rac1 activator Tiam1. The expression of the Rac1 inhibitor MgcRacGAP is decreased in double-KD cells, and the barrier development and Rac1 activation phenotypes are rescued by exogenous expression of MgcRacGAP. MgcRacGAP colocalizes with CGN and CGNL1 at TJs and forms a complex and interacts directly in vitro with CGN and CGNL1. Depletion of either CGN or CGNL1 in epithelial cells results in decreased junctional localization of MgcRacGAP but not of ECT2, a centralspindlin-interacting Rho GEF. These results provide new insight into coordination of Rho-family GTPase activities at junctions, since apical accumulation of CGN and CGNL1 at TJs during junction maturation provides a mechanism to spatially restrict down-regulation of Rac1 activation through the recruitment of MgcRacGAP.


2020 ◽  
Vol 22 (3) ◽  
pp. 353-353
Author(s):  
Halil Bagci ◽  
Neera Sriskandarajah ◽  
Amélie Robert ◽  
Jonathan Boulais ◽  
Islam E. Elkholi ◽  
...  

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

Author(s):  
Kevin Scharp ◽  
Stewart Shapiro ◽  
Bradley Armour-Garb

This chapter investigates the question of when it is reasonable to replace an inconsistent concept. After surveying a number of proposals for how one might understand constitutive principles, it goes on to endorse Burgess’s (2004) account of being pragmatically analytic, as a possible source of insight into constitutive principles. The chapter then raises a question: If truth is an inconsistent concept, does it need to be replaced? According to the argument in the chapter, when an inconsistent concept paralyzes valuable projects, it is time to replace it. And if we are to replace a concept, our replacement should be able to do the work that the inconsistency-yielding one did. This, of course, raises a fundamental question concerning what work the notion of truth does for us. The chapter mounts a case for the claim that inflationists, but not obvious deflationists, about truth should offer a replacement for the concept of truth.


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

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