The Protein Network of Reversal Clock in Myxobacteria

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The Protein Network of Reversal Clock in
Myxobacteria

• Yilin Wu, Yi Jiang, Mark Alber
• 08/31/2006

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Introduction Life cycle of Myxobacteria (Dale
Kaiser, 2003 )
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C-signal level controls the life cycle

• Gliding Motility polarity reverses regularly

(Dale Kaiser,2003)
Reversal and C-signaling (experiments) 1.
Cell contact signaling (C-signal) C-signal
protein is surface associated protein, localized
to cell ends and transmitted by end-to-end
contact. 2. C-signal level increases
monotonically during the cell life cycle. The
increased signal level first enhances reversal
frequency in rippling stage and then decreases it
in aggregation stage.
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Frz protein system regulates the reversal clock
P phosphorylated form Me methylated form FrzF
the active form
(Igoshin, Current Biology 2004)
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Frz protein system regulates the reversal clock

• Igoshin et al (PNAS, 2004) proposed the
  following reaction equations
• FrzF activationdeactivation f
  FrzF/(FrzF FrzF)
• FrzCD methylationdemethylation c
  FrzCD-M/(FrzCDFrzCD-M)
• FrzE phosphorylationdephosphorylation
  eFrzE-P/(FrzEFrzE-P)
• ?

(C-signal is modeled as a square pulse contained
in ka The second term is from the negative
feedback loop)
(Referred to the paper A model for a Network of
Phosphorylation-dephosphorylation Cycles
Displaying the Dynamics of Dominoes and Clocks,
D. Gonze and A. Goldbeter, J. Theor. Biol. 2001.)
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Results (Igoshin et al, PNAS 2004)

• Oscillation of the Frz-protein stystem

Oscillation frequency VS signaling strength
(defined as the maximum activation rate of FrzF
FruA-P activates more and more FrzF as C-signal
level increases.)
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Results (continued)

• Reproduced the reversal clock, and verifies the
  refractory period during the decreasing stage
  of active FrzF.
• Reproduce the C-signal strength dependence of
  reversal frequency as the developmental time goes.

Problems

• The key component in the model is the
  hypothetical negative feedback from FrzE-P to
  FrzF. It has not been verified in experiments
  yet.
• The parameters of rate are carefully picked.
• Recent experiments have found much more proteins
  involved in the reversal clock this model did
  not take into account any.

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Future plan

• Construct a more complete protein network for
  reversal clock, and try to avoid the artificial
  negative feedback. Hope to understand the
  reversal clock more precisely.

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FrzCD
C-signal------gt
Appendix A draft protein network from
literature survey
Ref. 1
FrzE-CheY?S-motility FrzE-CheA?A-motility
Reversal
AglZ?A-motility Ref. 3 Mask?S-motility Ref. 4
FrzS??? S-motility reversal Ref. 5
MglAGTP Ref. 2
Cgl?A-motility Tgl?S-motility
Has evidence of oscillation Ref. 5
Reversal
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References

• 1 Yinuo Li, et al. Divergent Regulatory
  Pathways Control A and s motility in Myxococcus
  xanthus through FrzE, a CheA-CheY Fusion Protein.
  2005
• 2 Alfred Spormann and Dale Kaiser. Gliding
  mutants of Myxococcus xanthus with high reversal
  frequencies and small displacements. 1999
• 3 Ruifeng Yang, et al. AglZ is a
  filament-formaing coiled-coil protein required
  for advanturous gliding motility of Myxococcus
  xanthus. 2004
• 4 Bobbie Thomasson, et al. MglA, a small
  GTPase, interacts with a tyrosine kinase to
  control type IV pili mediated motility and
  development of Myxococcus xanthus. 2002
• 5 Tam Mignot, et al. Regulated pole-to-pole
  oscillations of a bacterial gliding motility
  protein. 2005