Min System

One model of Z-ring formation permits its formation only after a certain spatial signal that tells the cell that it is big enough to divide.[3] The MinCDE system prevents FtsZ polymerization near certain parts of the plasma membrane. MinD localizes to the membrane only at cell poles and contains an ATPase and an ATP-binding domain. MinD is only able to bind to the membrane when in its ATP-bound conformation. Once anchored, the protein polymerizes, resulting in clusters of MinD. These clusters bind and then activate another protein called MinC, which has activity only when bound by MinD.[4] MinC serves as a FtsZ inhibitor that prevents FtsZ polymerization. The high concentration of a FtsZ polymerization inhibitor at the poles prevents FtsZ from initiating division at anywhere but the mid-cell.[5]

MinE is involved in preventing the formation of MinCD complexes in the middle of the cell. MinE forms a ring near each cell pole. This ring is not like the Z-ring. Instead, it catalyzes the release of MinD from the membrane by activating MinD's ATPase. This hydrolyzes the MinD's bound ATP, preventing it from anchoring itself to the membrane.

MinE prevents the MinD/C complex from forming in the center but allows it to stay at the poles. Once the MinD/C complex is released, MinC becomes inactivated. This prevents MinC from deactivating FtsZ. As a consequence, this activity imparts regional specificity to Min localization.[6] Thus, FtsZ can form only in the center, where the concentration of the inhibitor MinC is minimal. Mutations that prevent the formation of MinE rings result in the MinCD zone extending well beyond the polar zones, preventing FtsZ to polymerize and to perform cell division.[7] MinD requires a nucleotide exchange step to re-bind to ATP so that it can re-associate with the membrane after MinE release. The time lapse results in a periodicity of Min association that may yield clues to a temporal signal linked to a spatial signal. In vivo observations show that the oscillation of Min proteins between cell poles occurs approximately every 50 seconds.[8] Oscillation of Min proteins, however, is not necessary for all bacterial cell division systems. Bacillus subtilis has been shown to have static concentrations of MinC and MinD at the cell poles.[9] This system still links cell size to the ability to form a septum via FtsZ and divide.

MinD (cyan) chased by MinE (magenta) to form spiraling waves on an artificial membrane

The dynamic behavior of Min proteins has been reconstituted in vitro using artificial lipid bilayers,[10] with varying lipid composition[11] and different confinement geometry[12] as mimics for the cell membrane. The first pattern to be reconstituted were spiraling waves of MinD chased by MinE,[13] followed by the reconstitution of waves of all three proteins, MinD, MinE and MinC.[14] Importantly, MinD and MinE can self-organize into a wide variety of patterns depending on the reaction conditions.[15][16]

Additional study is required to elucidate the extent of temporal and spatial signaling permissible by this biological function. These in vitro systems offered unprecedented access to features such as residence times and molecular motility.