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Tostevin, Filipe ORCID logoORCID: https://orcid.org/0000-0002-2263-2135; Wigbers, Manon ORCID logoORCID: https://orcid.org/0000-0003-4732-2878; Søgaard-Andersen, Lotte ORCID logoORCID: https://orcid.org/0000-0002-0674-0013 and Gerland, Ulrich ORCID logoORCID: https://orcid.org/0000-0002-0859-6422 (2021): Four different mechanisms for switching cell polarity.
In: PLOS Computational Biology 17(1), e1008587 [PDF, 2MB]

Abstract

The mechanisms and design principles of regulatory systems establishing stable polarized protein patterns within cells are well studied. However, cells can also dynamically control their cell polarity. Here, we ask how an upstream signaling system can switch the orientation of a polarized pattern. We use a mathematical model of a core polarity system based on three proteins as the basis to study different mechanisms of signal-induced polarity switching. The analysis of this model reveals four general classes of switching mechanisms with qualitatively distinct behaviors: the transient oscillator switch, the reset switch, the prime-release switch, and the push switch. Each of these regulatory mechanisms effectively implements the function of a spatial toggle switch, however with different characteristics in their nonlinear and stochastic dynamics. We identify these characteristics and also discuss experimental signatures of each type of switching mechanism.

Author summary: Cell polarity is key to processes such as cell growth, division, differentiation, and motility. Polarity arises from asymmetric distributions of proteins in the cell. How asymmetric patterns develop from uniform protein distributions, has been studied extensively. However, it is less clear how cells can switch such protein patterns in response to a signal. Here, we identify four qualitatively different mechanisms for how a polar protein pattern can be reversed. For each mechanism, we describe experimental signatures permitting their identification in natural systems. By providing possible regulatory circuits for these mechanisms, we also offer blueprints for synthetic implementations of switchable cell polarity, in artificial or engineered cells.

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