title: Beyond symmetry-breaking: competition and negative feedback in GTPase regulation.
abstract: Cortical domains are often specified by the local accumulation of active GTPases. Such domains can arise through spontaneous symmetry-breaking, suggesting that GTPase accumulation occurs via positive feedback. Here, we focus on recent advances in fungal and plant cell models - where new work suggests that polarity-controlling GTPases develop only one 'front' because GTPase clusters engage in a winner-takes-all competition. However, in some circumstances two or more GTPase domains can coexist, and the basis for the switch from competition to coexistence remains an open question. Polarity GTPases can undergo oscillatory clustering and dispersal, suggesting that these systems contain negative feedback. Negative feedback may prevent polarity clusters from spreading too far, regulate the balance between competition and coexistence, and provide directional flexibility for cells tracking gradients.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Chi-Fang
authors.initials: CF
authors.lastname: Wu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lew
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics* / Q000502:physiology; D025461:Feedback, Physiological; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D059828:Plant Cells / Q000378:metabolism* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein
keywords: Cdc42; GAP; GEF; Rac; Rop