Highly Canalized MinD Transfer and MinE Sequestration Explain the Origin of Robust MinCDE-Protein Dynamics

Abstract

Min-protein oscillations in Escherichia coli are characterized by the remarkable robustness with which spatial patterns dynamically adapt to variations of cell geometry. Moreover, adaption, and therefore proper cell division, is independent of temperature. These observations raise fundamental questions about the mechanisms establishing robust Min oscillations, and about the role of spatial cues, as they are at odds with present models. Here, we introduce a robust model based on experimental data, consistently explaining the mechanisms underlying pole-to-pole, striped, and circular patterns, as well as the observed temperature dependence of the oscillation period. Contrary to prior conjectures, the model predicts that MinD and cardiolipin domains are not colocalized. The transient sequestration of MinE and highly canalized transfer of MinD between polar zones are the key mechanisms underlying oscillations. MinD channeling enhances midcell localization and facilitates stripe formation, revealing the potential optimization process from which robust Min-oscillations originally arose.

How do bacteria localize proteins to the cell pole?

“…in filamentous cells), the Min system adopts a striped localization pattern (Raskin and de Boer, 1999), suggesting that no polar feature is needed to obtain cycles of collective membrane binding and unbinding. Thus, the cell geometry and the MinD-MinE interplay at the membrane might be sufficient to explain pole-to-pole oscillations in vivo (Meinhardt and de Boer, 2001;Howard and Kruse, 2005;Varma et al, 2008;Di Ventura and Sourjik, 2011;Loose et al, 2011;Halatek and Frey, 2012). Consistent with this idea, Min proteins form spontaneous waves on artificial lipid layers in vitro (Loose et al, 2008).…”

“…After 'running out' of membrane-associated MinD-ATP dimers at one pole, MinE is released into the cytoplasm, diffuses until it associates with the edge of the new MinD-ATP dimer zone at the membrane (Steps 3 and 4). specific polar-nucleation protein such as cardiolipin, to which MinD preferentially binds (Mileykovskaya et al, 2003;Drew et al, 2005;Cytrynbaum and Marshall, 2007;Renner and Weibel, 2012), although the importance of such spatial cues is still under investigation (Halatek and Frey, 2012).…”

Protein Patterns and Oscillations on Lipid Monolayers and in Microdroplets

“…These pole‐to‐pole oscillations generate a time‐averaged non‐homogeneous concentration gradient with a minimum at the mid‐cell plane, the future cell division site 2, 3, 4, 5, 6, 7. Intriguingly, only a minimal set of components (the two membrane interacting proteins MinD and MinE, a lipid membrane, and ATP) has been shown to establish Min oscillations 8, 9, 10, 11, 12. The protein MinC follows the oscillating MinDE patterns by binding to MinD, and it directly inhibits the assembly of the cell‐division protein FtsZ at the poles 3, 7, 13, 14, 15.…”

Oscillation helps to get division right

“…One of the many strong points of the paper by Vecchiarelli et al (10) is that the new biochemical insight that emerges could not have been gleaned from classic ensemble biochemistry, or from models based on simulations of reaction-diffusion patterning mechanisms. Importantly, the paper discusses the fact that mechanistically diverse models, using different biochemical assumptions, can capture the same self-organizing oscillatory behavior using reaction-diffusion patterning mechanisms in which there is a single nonlinear protein interaction term (11)(12)(13)(14). This underlines the fact that modeling alone cannot inform biochemical mechanism and emphasizes the desirability of careful experimental studies and robust data if modeling is to capture biochemical detail.…”

“…For example, one family of models has the regulator MinE role being simply a binding partner for MinD ATP, with binding stimulating ATP hydrolysis and MinD release from the membrane (12). MinE alone interacts with membrane weakly to uncover its MinD interacting surface (7).…”