An immunogenic 24 kDa calcium binding protein is found in Trypanosoma cruzi and is termed flagellar calcium binding protein (FCaBP). FcaBP is modified by the addition of myristate and palmitate to its amino terminus. These modifications mediate its localization to the flagellar plasma membrane. Calcium binding is also required for localization. Thus, FcaBP is similar to recoverin a calcium-myristoyl switch protein of the mammalian retina. FcaBP binds calcium through the third and fourth EF hand domains in distinction from recoverin which is modified only by myristate and binds calcium through the second and third EF hand domains. FcaBP is a novel calcium-acyl switch protein. We will extend our studies of FcaBP in a five-year research effort, the Specific Aims of which are: (i) determination of the mechanism for the flagellar membrane localization of FcaBP, (ii) identification of FCaBP partner proteins, (iii) elucidation of the calcium-myristoly/palmitoyl switch mechanism and (iv) characterization of Typanosoma brucei calcium acyl switch proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI046781-01A1
Application #
6196484
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Fairfield, Alexandra
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
1
Fiscal Year
2000
Total Cost
$330,750
Indirect Cost
Name
Northwestern University at Chicago
Department
Pathology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Emmer, Brian T; Daniels, Melvin D; Taylor, Joann M et al. (2010) Calflagin inhibition prolongs host survival and suppresses parasitemia in Trypanosoma brucei infection. Eukaryot Cell 9:934-42
Emmer, Brian T; Maric, Danijela; Engman, David M (2010) Molecular mechanisms of protein and lipid targeting to ciliary membranes. J Cell Sci 123:529-36
Maric, Danijela; Epting, Conrad L; Engman, David M (2010) Composition and sensory function of the trypanosome flagellar membrane. Curr Opin Microbiol 13:466-72
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Tyler, Kevin M; Fridberg, Alina; Toriello, Krista M et al. (2009) Flagellar membrane localization via association with lipid rafts. J Cell Sci 122:859-66
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Fridberg, Alina; Olson, Cheryl L; Nakayasu, Ernesto S et al. (2008) Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei. J Cell Sci 121:522-35
Fridberg, Alina; Buchanan, Kathryn T; Engman, David M (2007) Flagellar membrane trafficking in kinetoplastids. Parasitol Res 100:205-12

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