In general, mediators of bacterial cell shape via the cytoskeleton are not well understood. We will explore the interplay of the cytoskeleton and cell shape based on three promising observations. First, we have identified a phospholipid synthase (CC1159) that, when overexpressed, causes the bacterium Caulobacter crescentus to change its shape from a crescent to a rod-shaped morphology by inhibiting the localization and function of the intermediate filament protein known as crescentin. Second, overexpression of a catalytically inactive version of the phospholipid synthase still mediates the change in cell shape, suggesting that the phenotype results from a protein-protein interaction instead of elevated levels of a phospholipid. Third, bacterial two-hybrid data suggest that our phospholipid synthase interacts with itself and with cytosine triphosphate synthase (CtpS), which also induces a rod-shaped morphology when overexpressed via interaction with crescentin. Human homologs of crescentin, the intermediate filament nuclear Lamins A/C, are implicated in premature aging and muscular dystrophy, and we suggest a link between phospholipid synthesis and intermediate filaments in C. crescentus that may parallel their human homologs. Research in the eukaryotic literature is just starting to link phospholipids/sphingolipids [and glycosylphosphatidylinositol-anchored proteins (GPI-AP)] with intermediate filaments, suggesting that our investigations in C. crescentus may be relevant to humans. Additionally, Helicobacter pylori's and Vibrio cholerae's crescent shape contributes to host colonization and pathogenesis. Thus, our findings may be also relevant to cell shape and pathogenicity of these human pathogens.

Public Health Relevance

Premature aging and muscular dystrophy result from dysfunctional intermediate filaments (IF), whose function are poorly understood due to the presence of multiple IFs with redundant function in human cells. In the model organism Caulobacter crescentus, which only contains one IF, we have discovered that the overexpression of a protein (that makes a component of the cell membrane) prevents the proper localization and function of Caulobacter's IF. In this proposal, we aim to identify the function of this cell-membrane-related protein and to create a model that illustrates how other proteins can effect IF function.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Continuance Award (SC3)
Project #
1SC3GM121234-01A1
Application #
9417929
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Rubio, Mercedes
Project Start
2018-05-01
Project End
2022-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
California State University Northridge
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
055752331
City
Northridge
State
CA
Country
United States
Zip Code
91330