The PAR network: redundancy and robustness in a symmetry-breaking system.
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.
Temasek Lifesciences Laboratory, National University of Singapore, , 1 Research Link, Singapore 117604, Republic of Singapore.
Fumio
F
Motegi
Geraldine
G
Seydoux
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D018385:Centrosome / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015053:Zygote / Q000502:physiology; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C409406:PAR-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
Cdc42; PAR proteins; feedback loops; modelling of biological networks; polarity; robustness