Independence of symmetry breaking on Bem1-mediated autocatalytic activation of Cdc42.
The ability to break symmetry and polarize through self-organization is a fundamental feature of cellular systems. A prevailing theory in yeast posits that symmetry breaking occurs via a positive feedback loop, wherein the adaptor protein Bem1 promotes local activation and accumulation of Cdc42 by directly tethering Cdc42(GTP) with its guanine nucleotide exchange factor (GEF) Cdc24. In this paper, we find that neither Bem1 nor the ability of Bem1 to bind Cdc42(GTP) is required for cell polarization. Instead, Bem1 functions primarily by boosting GEF activity, a role critical for polarization without actin filaments. In the absence of actin-based transport, polarization of Cdc42 is accomplished through Rdi1, the Cdc42 guanine nucleotide dissociation inhibitor. A mathematical model is constructed describing cell polarization as a product of distinct pathways controlling Cdc42 activation and protein localization. The model predicts a nonmonotonic dependence of cell polarization on the concentration of Rdi1 relative to that of Cdc42.
Stowers Institute for Medical Research, Kansas City, MO, 64110.
Sarah E
SE
Smith
Boris
B
Rubinstein
Inês
I
Mendes Pinto
Brian D
BD
Slaughter
Jay R
JR
Unruh
Rong
R
Li
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016764:Cell Polarity; D003593:Cytoplasm / Q000378:metabolism; D025461:Feedback, Physiological; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008962:Models, Theoretical; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C073594:CDC24 protein, S cerevisiae; D018797:Cell Cycle Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D020662:Guanine Nucleotide Exchange Factors; C534963:Rdi1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C073129:BEM1 protein, S cerevisiae; D006160:Guanosine Triphosphate; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae