Faculty Research Page
Professor of the Graduate School Division of Biochemistry, Biophysics and Structural BiologyLab Homepage: http://mcb.berkeley.edu/labs/zusman/
The focus of our research is to determine how signal transduction regulates directed motility and behavior in the bacterium Myxococcus xanthus using an integrated approach that combines biochemistry, genetics, and cell biology. M. xanthus is an excellent model system to address fundamental questions concerning cell-cell signaling and directed movement as cells form multicellular biofilms and fruiting bodies as part of a complex life cycle. Previously, we have shown that the Frz signal transduction pathway regulates both vegetative swarming and developmental aggregation by controlling the reversal frequency of cells. We hypothesize that M. xanthus, like E. coli and other chemotaxing bacteria, control directional movements by temporal sensing of stimuli and biasing directional motility. We remain focused on the Frz system since it is probably the master regulator of directional control in this organism. This pathway has multiple inputs and multiple outputs, which are all coordinated. We are trying to understand the nature of these input and output signals, their regulation and how they control the two engines of gliding motility.
Myxococcus is a gliding bacterium that contains two motility systems: S-motility, powered by polar type IV pili, and A-motility, powered by uncharacterized motors and adhesion complexes. The localization and coordination of the two motility engines is essential for directed motility as cells move forward and reverse. During cell reversals, the polarity and localization of motility proteins are rapidly inverted, rendering this system a fascinating example of dynamic protein localization. For example, during periodic cell reversals, type IV pili are disassembled at one pole and reassembled at the other pole. Accompanying these reversals, FrzS, a protein required for S-motility swarming, moves in an oscillatory pattern between the cell poles. The frequency of the oscillations is controlled by the Frz chemosensory system, which is essential for directed motility. Pole-to-pole migration of FrzS appears to involve movement along a filament running the length of the cell. FrzS dynamics may thus regulate cell polarity during directed motility.
We are also studying the localization of A-motility proteins. For example, AglZ, a protein similar in structure to FrzS, is required for A-motility but not S-motility. AglZ-YFP localization was followed in live cells. Fully motile cells showed AglZ-YFP to be present in clusters distributed in an ordered array spanning the cell length. As cells moved forward, these clusters maintained fixed positions with respect to the agar surface, rather than to their relative positions in the cell. Interestingly, the only AglZ-YFP cluster that moved relative to the cell body was the one located at the leading pole, suggesting that new clusters were assembled at the leading pole. Upon cellular reversal, AglZ localized rapidly to the new leading pole, and as cells began to move, localized to distributed clusters. These results suggest an alternative mechanism for A-motility whereby intracellular motor complexes that connect to membrane spanning adhesion complexes and to the cytoskeleton power motility by pushing against the substratum moving the cell body forward.
Frz pathway mutants are defective in vegetative swarming and developmental aggregation because they cannot control cell reversals. We have made significant progress in defining the various genes of the Frz chemosensory system and have characterized many of the essential components necessary for their function. For example, several key signaling proteins contain regulatory domains that control methylation and phosphorylation. We have been using cell biology techniques to study the localization of chemosensory proteins like FrzCD, a cytoplasmic receptor. FrzCD does not form membrane bound polar clusters typical for most bacteria, but rather cytoplasmic clusters that are helically arranged and span the cell length. These clusters continuously change their position, number, and intensity as cells move forward and reverse.
Gliding Motility Revisited: How do the myxobacteria move without flagella? [E.M.F. Mauriello, T. Mignot., Z. Yang, and D.R. Zusman (2010). Microbiol. and Molec. Biol. Revs, 74: 229-249.
A Multi-protein complex from Myxococcus xanthus required for bacterial gliding motility. [B. Nan, E.M.F. Mauriello, Wong, A., Sun, I.-H., and D.R. Zusman (2010). Molec. Microbiol., 76: 1539-1554]
Bacterial motility complexes require the actin-like protein, MreB and the Ras homologue, MglA. [E.M.F. Mauriello, F. Mouhamar, B.Nan, A. Ducret, D. Dai, D.R. Zusman* and T. Mignot* (2010). EMBO J., 29: 315-326]
AglZ regulates adventurous (A-) motility in Myxococcus xanthus through its interaction with the cytoplasmic receptor, FrzCD. [ E.M.F. Mauriello, B. Nan, and D.R. Zusman (2009). Molec. Microbiol., 72: 964-977]
Localization of a bacterial cytoplasmic receptor is dynamic and changes with cell-cell contacts. [E.M.F. Mauriello, D.P. Astling, O. Sliusarenko, and D.R. Zusman (2009). Proc. Natl. Acad. Sci., USA., 106: 4852-4857]
Site-specific receptor methylation of FrzCD in Myxococcus xanthus is controlled by a tetra-trico peptide repeat (TPR) containing regulatory domain of the FrzF methyltransferase. [A.E. Scott, E. Simon, S.K. Park, P. Andrews, and D.R. Zusman (2008) Molec. Microbiol., 69: 724-735]
The receiver domain of FrzE, a CheA-CheY fusion protein, regulates the CheA histidine kinase activity and downstream signaling to the A- and S-motility systems of Myxococcus xanthus. [Y.F. Inclán, S. Laurent, and D.R. Zusman (2008) Molec. Microbiol. 68: 1328-1339]
EspA, an orphan hybrid protein kinase, regulates the timing of expression of key developmental proteins of Myxococcus xanthus. [P.I. Higgs, S. Jagadeesan, P. Mann, and D.R. Zusman (2008) J. Bacteriol. 190: 4416-4426]
Evidence that Focal Adhesion Complexes Power Bacterial Gliding Motility. [T. Mignot, J.W. Shaevitz, P. Hartzell, and D.R. Zusman (2007) Science 315: 853-856]
FrzZ, a dual CheY-like response regulator, functions as an output for the Frz chemosensory pathway of Myxococcus xanthus. [Y.F. Inclán, H. Vlamakis, and D.R. Zusman (2007) Molecular Microbiol., 65: 90-102]
Two localization motifs mediate polar residence of FrzS during cell movement and reversals of Myxococcus xanthus. [T. Mignot, T.,, J.P. Merlie, Jr., and D.R. Zusman (2007) Molecular Microbiol., 65: 363-372]
An atypical receiver domain controls the dynamic polar localization of the Myxococcus xanthus social motility protein FrzS. [J.S. Fraser, J.P. Merlie Jr., N. Echols, S.R. Weisfield, T. Mignot, D.E. Wemmer, D.R. Zusman and T. Alber (2007) Molec. Microbiol., 65: 317-332]
Two Ser/Thr protein kinases essential for efficient aggregation and spore morphogenesis in Myxococcus xanthus. [E.A. Stein, K. Cho, P.I. Higgs and D.R. Zusman (2006) Molec. Microbiol. 60: 1414-1431]
Regulated pole-to-pole oscillations of a bacterial gliding motility protein. [T. Mignot, J.P. Merlie, Jr. and D.R. Zusman (2005) Science 310: 855-857]
Photo credit: Mark Joseph Studios
Last Updated 2010-07-23