Faculty Research Page

David Zusman

David Zusman

Professor Emeritus of Biochemistry, Biophysics and Structural Biology

Lab Homepage: http://mcb.berkeley.edu/labs/zusman/

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Research Interests

The focus of our research has been 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 hypothesized that M. xanthus, like E. coli and other chemotaxing bacteria, control directional movements by temporal sensing of stimuli and biasing directional motility. We remained 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 were trying to understand the nature of these input and output signals, their regulation and how they control the two engines of gliding motility. 

Current Projects

In the last few years we have been studying the motor proteins that power gliding motility in M. xanthus. The motor proteins interact with the Frz chemosensory system and with MreB, an actin homolog. The Frz system regulates cell polarity through MglA, a Ras family GTPase. We examined the localization and dynamics of MglA and the gliding motors in high spatial and time resolution. We determined that MglA localizes not only at the cell poles, but also along the cell bodies, forming a decreasing concentration gradient toward the lagging cell pole. MglA directly interacts with the motor protein AglR, and the spatial distribution of AglR reversals is positively correlated with the MglA gradient. Thus, the motors moving toward lagging cell poles are less likely to reverse, generating stronger forward propulsion.

Selected Publications

The polarity of myxobacterial gliding is regulated by direct interactions between the gliding motors and the Ras homolog MglA.  [B. Nan,  J.N. Bandaria, K.Y. Guo, X. Fan, A. Moghtaderi, A. Yildiz, and D.R. Zusman (2014). Proc. Natl. Acad. Sci., USA.  doi: 10.1073/pnas.1421073112]
Functional organization of a multimodular bacterial chemosensory apparatus. [A. Moine,  R. Agrebi, L. Espinosa, J.R. Kirby, D.R. Zusman, T. Mignot and E.M.F. Mauriello (2014). PLoS Genetics, 10: e1004164. doi: 10.1371]
Bacteria that glide with helical tracks. [B. Nan, M.J. McBride, J. Chen, D.R. Zusman, and G. Oster (2014). Current Biology, 24: R169-R173. doi: 10.1016]
Phosphorylation-dependent localization of the response regulator FrzZ signals cell reversals in Myxococcus xanthus. [C. Kaimer, and D.R. Zusman (2013). Molec. Microbiol., 88: 740-753]
Flagella stator homologues function as motors for myxobacterial gliding motility by moving in helical trajectories. [B. Nan, J.N. Bandaria, A. Moghtaderi, I-H. Sun, A. Yildiz and D.R. Zusman. (2013). Proc. Natl. Acad. Sci., USA, 110: E1508-13]
Uncovering the mystery of gliding motility in the myxobacteria. B. Nan, and D.R. Zusman (2011). Ann. Rev. Gen., 45: 21-39]
FrzS regulates social motility in Myxococcus xanthus by controlling exopolysaccharide production [J.E. Berleman, J.J. Vicente, A.E. Davis, S.Y. Jiang, Y.E. Seo, and D.R. Zusman (2011). PLoS One, 6: e23920, p. 1-10]
Myxobacteria gliding motility requires cytoskeleton rotation powered by proton motive force [B. Nan, J. Chen, J.C. Neu, R.M. Berry, G. Oster and D.R. Zusman (2011). Proc. Natl. Acad. Sci., USA, 108: 2498-2503]
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]
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 Hanson at Mark Joseph Studios.

Last Updated 2015-08-26