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Philos Trans R Soc Lond B Biol Sci. 2013 Sep 23;368(1629):20130010. doi: 10.1098/rstb.2013.0010. Print 2013.

The PAR network: redundancy and robustness in a symmetry-breaking system.

Author information

1
Temasek Lifesciences Laboratory, National University of Singapore, , 1 Research Link, Singapore 117604, Republic of Singapore.

Abstract

To become polarized, cells must first 'break symmetry'. Symmetry breaking is the process by which an unpolarized, symmetric cell develops a singularity, often at the cell periphery, that is used to develop a polarity axis. The Caenorhabditis elegans zygote breaks symmetry under the influence of the sperm-donated centrosome, which causes the PAR polarity regulators to sort into distinct anterior and posterior cortical domains. Modelling analyses have shown that cortical flows induced by the centrosome combined with antagonism between anterior and posterior PARs (mutual exclusion) are sufficient, in principle, to break symmetry, provided that anterior and posterior PAR activities are precisely balanced. Experimental evidence indicates, however, that the system is surprisingly robust to changes in cortical flows, mutual exclusion and PAR balance. We suggest that this robustness derives from redundant symmetry-breaking inputs that engage two positive feedback loops mediated by the anterior and posterior PAR proteins. In particular, the PAR-2 feedback loop stabilizes the polarized state by creating a domain where posterior PARs are immune to exclusion by anterior PARs. The two feedback loops in the PAR network share characteristics with the two feedback loops in the Cdc42 polarization network of Saccharomyces cerevisiae.

KEYWORDS:

Cdc42; PAR proteins; feedback loops; modelling of biological networks; polarity; robustness

PMID:
24062581
PMCID:
PMC3785961
DOI:
10.1098/rstb.2013.0010
[Indexed for MEDLINE]
Free PMC Article

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