Metazoan development is characterized by the specialization of cells which, functioning in harmony, allow for the growth and survival of the organism as a whole. The ultimate goal of this research is to understand the components which regulate the spacial and temporal organization of a multicellular organism. Toward this goal, we propose to continue studies of 117 antigen, a surface protein apparently involved in cell cohesion of D. discoideum amoebae.
The Specific Aims are directed toward tow complementary objectives. One is to define the antigen in biochemical terms and thus understand the features which contribute to its cell surface expression and function. The other is to understand the role of the antigen in morphogenesis.
The specific Aims are to: 1. Characterize the PI-G tail of 117 antigen. 2. Examine the endogenous enzyme activity responsible for the release of 117 antigen and its physiological role. 3. Study 117 antigen developmental regulation and function. We have documented that 117 antigen possess a number of unusual modifications, including a glycolipid structure (PI-G tail) that anchors the protein to the cello surface. The biological significance of that structure is realized by the presence of an endogenous enzyme capable of releasing the antigen into the medium as part of the cells developmental cycle. This developmental cycle involves the cyclic expression of 117 antigen, underscoring its importance in morphogenesis. Continued studies of the antigen are expected to expand significantly our knowledge of how cells regulate surface levels of specific proteins and do so in a cyclic manner. This plasticity of expression reflects a more usual mechanism of regulation which may be fundamental to the morphogenesis of a multicellular organism.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM034561-04A1
Application #
3285810
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1985-09-05
Project End
1994-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Pauly, P C; Klein, C (1996) An uncleaved glycosylphosphatidylinositol signal mediates Ca(2+)-sensitive protein degradation. Biochem J 317 ( Pt 2):533-40
Pauly, P C; Klein, C (1995) Lack of glycosyl-phosphatidylinositol anchoring leads to precursor retention by a unique mechanism in Dictyostelium discoideum. Biochem J 306 ( Pt 3):643-50
Souza, G M; Klein, C; Maia, J C et al. (1994) Calcium uptake and gp80 messenger RNA destabilization follows cAMP receptor down regulation in Dictyostelium discoideum. Cell Signal 6:883-95
da Silva, A M; Klein, C (1991) Biochemical and functional characterization of a glycolipid anchored cell adhesion molecule in Dictyostelium discoideum. Cell Biol Int Rep 15:1065-82
da Silva, A M; Klein, C (1990) Cell adhesion in transformed D. discoideum cells: expression of gp80 and its biochemical characterization. Dev Biol 140:139-48
da Silva, A M; Klein, C (1990) A rapid posttranslational myristylation of a 68-kD protein in D. discoideum. J Cell Biol 111:401-7
Juliani, M H; Souza, G M; Klein, C (1990) cAMP stimulation of Dictyostelium discoideum destabilizes the mRNA for 117 antigen. J Biol Chem 265:9077-82
da Silva, A M; Klein, C (1989) Characterization of a glycosyl-phosphatidylinositol degrading activity in Dictyostelium discoideum membranes. Exp Cell Res 185:464-72
Browne, L H; Sadeghi, H; Blumberg, D et al. (1989) Re-expression of 117 antigen, a cell surface glycoprotein of aggregating cells, during terminal differentiation of Dictyostelium discoideum prespore cells. Development 105:657-64
Kraft, B; Chandrasekhar, A; Rotman, M et al. (1989) Dictyostelium erasure mutant HI4 abnormally retains development-specific mRNAs during dedifferentiation. Dev Biol 136:363-71

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