Unequal cell division is a central mechanism in the generation of new cell types. In Caulobacter crescentus differentiation is the direct result of repeated, asymmetric cell division and this aquatic bacterium provides an ideal model for elucidating the mechanisms underlying developmental control. The patterns of differentiation and cell cycle progression in these cells are closely coordinated by two- component signal transduction systems. Possibly unique aspects of these two-component proteins is the fact that they respond to internal cell cycle cues instead of environmental conditions and some of them are essential for division and cell viability. The organization of the signal transduction pathways is not fully defined, however, and how these pathways coordinate the precise temporal and spatial patterns of developmental events during the cell cycle is far from clear. Experiments described in the proposal are designed to address the following goals: I. Identify and characterize components in the essential signal transduction pathway, DivJ => DivK => X => CtrA, which regulates cell cycle progression and differentiation; 2. Determine how the essential response regulator DivK functions in a signal transduction pathway(s) to control both cell division and motility; 3. Characterize mechanism of action and function of tyrosine kinase DivL in signal transduction; 4. Analyze the roles of histidine kinase DivJ and response regulator PleD in establishing cellular polarity; and 5. Examine the regulation of cell division genes in vivo by the essential signal transduction pathway responsible for phosphorylation and activation of CtrA.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM058794-03
Application #
6343060
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Zatz, Marion M
Project Start
1999-01-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
3
Fiscal Year
2001
Total Cost
$309,484
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Sciochetti, Stephen A; Ohta, Noriko; Newton, Austin (2005) The role of polar localization in the function of an essential Caulobacter crescentus tyrosine kinase. Mol Microbiol 56:1467-80
Ohta, Noriko; Newton, Austin (2003) The core dimerization domains of histidine kinases contain recognition specificity for the cognate response regulator. J Bacteriol 185:4424-31
Guillet, Valerie; Ohta, Noriko; Cabantous, Stephanie et al. (2002) Crystallographic and biochemical studies of DivK reveal novel features of an essential response regulator in Caulobacter crescentus. J Biol Chem 277:42003-10
Sciochetti, Stephen A; Lane, Todd; Ohta, Noriko et al. (2002) Protein sequences and cellular factors required for polar localization of a histidine kinase in Caulobacter crescentus. J Bacteriol 184:6037-49
Wu, J; Ohta, N; Zhao, J L et al. (1999) A novel bacterial tyrosine kinase essential for cell division and differentiation. Proc Natl Acad Sci U S A 96:13068-73