Final Report Summary - DOME (Dissecting a Novel Mechanism of Cell Motility)
In the course of the ERC grant period, we have elucidated the motility mechanism for the first time. The motility complex (named Agl-Glt) is a multi-tiered protein complex that assembles in the bacterial envelope. The assembly occurs at the leading cell pole of the bacterium by direct recruitment to the bacterial actin cytoskeleton (MreB) via the small Ras-like protein MglA. The complex then moves directionally toward the lagging cell pole, propelling the cell as it attaches the underlying surface via outer membrane adhesion factors. We have precisely identified the motor complex and shown that it moves along a helical track in the cell envelope. Thus, the cell rotates along its longitudinal axis as it moves forward. At the lagging cell pole, the motility complex is disassembled, simply by disrupting the interaction between MglA and actin. MglA and its regulator MglB act at the corner of assembly and regulation because their localization can be switched synchronously to the opposite cell pole (reversal), provoking movement in the opposite direction. We identified critical factors underlying this regulation. Specifically, the localization of MglA is regulated by a receptor/kinase chemosensory-type complex (Frz). In this process the kinase phosphorylates two spatial regulators that act sequentially to target of MglA to the pole and detach it when reversal signals are emitted by the kinase. Thus, the cell polarity of Myxococcus cells can be switched by signal transduction acting like a molecular compass in response to environmental signals.
The discovery of the Myxococcus motility complex and its regulation shed light on the evolutionary origin of motility in bacteria and revealed that it emerged by a three-step process where an ancestral bacterial signaling pathway (Frz) first recruited a eukaryotic-type G-protein module (MglAB), which subsequently recruited the motility complex (Agl-Glt). The motility complex itself evolved recently from an ancient molecular complex that is widespread in bacteria. However, these complexes are likely not motility complexes because they lack proteins, which we find are critical for motility. In fact, we studied the function of one of these complexes as one of them (Agl-Nfs) is also encoded by the Myxococcus genome in addition to the motility apparatus. We found that Agl-Nfs assembles specifically in Myxococcus spores and promotes assembly of the polysaccharidic spore coat. Similar to the motility complex the Agl-Nfs complex moves along the spore cell envelope, but in this case because the outer parts of the complex are directly linked to the main spore coat polymer, this movement winds the spore coat around the spore envelope. Thus, the Myxococcus motility complex could have emerged from a new class of bacterial cell envelope assembly system. Investigating the function of related complex will be an important post-ERC direction because it may explain fundamentally how large macromolecular complexes evolve for specific tasks, a major question in biology.