Dynamic Opposition of Clustered Proteins Stabilizes Cortical Polarity in the C. elegans Zygote.
Dev Cell
; 35(1): 131-42, 2015 Oct 12.
Article
em En
| MEDLINE
| ID: mdl-26460948
ABSTRACT
Dynamic maintenance of cell polarity is essential for development and physiology. Here we combine experiments and modeling to elucidate mechanisms that maintain cortical polarity in the C. elegans zygote. We show that polarity is dynamically stabilized by two coupled cross-inhibitory feedback loops one involves the oligomeric scaffold PAR-3 and the kinase PAR-1, and the other involves CDC-42 and its putative GAP CHIN-1. PAR-3 and CDC-42 are both required locally to recruit PAR-6/PKC-3, which inhibits PAR-1 (shown previously) and inhibits local growth/accumulation of CHIN-1 clusters. Conversely, PAR-1 inhibits local accumulation of PAR-3 oligomers, while CHIN-1 inhibits CDC-42 (shown previously), such that either PAR-1 or CHIN-1 can prevent recruitment of PAR-6/PKC-3, but loss of both causes complete loss of polarity. Ultrasensitive dependence of CHIN-1 cluster growth on PAR-6/PKC-3 endows this core circuit with bistable dynamics, while transport of CHIN-1 clusters by cortical flow can stabilize the AP boundary against diffusive spread of PAR-6/PKC-3.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Zigoto
/
Polaridade Celular
/
Caenorhabditis elegans
/
Regulação da Expressão Gênica no Desenvolvimento
/
Proteínas de Caenorhabditis elegans
/
Embrião não Mamífero
Limite:
Animals
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos