title: Dynamic Opposition of Clustered Proteins Stabilizes Cortical Polarity in the C. elegans Zygote.
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.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Sailer
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Anneken
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA; Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Younan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, WI 53792, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA; Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, IL 60637, USA; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA; Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: emunro@uchicago.edu.
authors.forename: Edwin
authors.initials: E
authors.lastname: Munro
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000166:cytology* / Q000378:metabolism
chemical_list: C547941:CHIN-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; C081779:cdc-42 protein, C elegans; C512642:par-6 protein, C elegans; C409406:PAR-1 protein, C elegans; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C; D019204:GTP-Binding Proteins