Abstract

Cells of Dictyostelium discoideum are single amoeboid phagocytes. During the vegetative stage cells are chemotactic toward folic acid and during the aggregative stage toward extracellular cAMP. This cell is widely used as a model for amoeboid chemotaxis. From a number of studies it is clear that actin polymerization is stimulated by chemoattractant and that this is temporally correlated with pseudopod extension toward the source of chemoattractant. The general goal of this proposal is to determine how chemotactic stimulation is coupled to actin polymerization. We will investigate this by developing in vitro assays for ligand stimulated actin polymerization that is physiologically relevant to chemotaxis. We will then use these assays to investigate the molecular mechanism of coupling of actin polymerization to stimulation with chemoattractant. This investigation will include experiments using drugs and antibodies to modulate in vitro activity and eventual isolation of the ligand stimulated nucleation activity for actin polymerization.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM038511-05
Application #
3294959
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1988-02-01
Project End
1993-09-29
Budget Start
1992-02-01
Budget End
1993-09-29
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Isaac, Beth M; Ishihara, Dan; Nusblat, Leora M et al. (2010) N-WASP has the ability to compensate for the loss of WASP in macrophage podosome formation and chemotaxis. Exp Cell Res 316:3406-16
Cammer, Michael; Gevrey, Jean-Claude; Lorenz, Mike et al. (2009) The mechanism of CSF-1-induced Wiskott-Aldrich syndrome protein activation in vivo: a role for phosphatidylinositol 3-kinase and Cdc42. J Biol Chem 284:23302-11
Oser, Matthew; Condeelis, John (2009) The cofilin activity cycle in lamellipodia and invadopodia. J Cell Biochem 108:1252-62
Oser, Matthew; Yamaguchi, Hideki; Mader, Christopher C et al. (2009) Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. J Cell Biol 186:571-87
Desmarais, Vera; Yamaguchi, Hideki; Oser, Matthew et al. (2009) N-WASP and cortactin are involved in invadopodium-dependent chemotaxis to EGF in breast tumor cells. Cell Motil Cytoskeleton 66:303-16
Leyman, Shirley; Sidani, Mazen; Ritsma, Laila et al. (2009) Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering. Mol Biol Cell 20:4509-23
Philippar, Ulrike; Roussos, Evanthia T; Oser, Matthew et al. (2008) A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev Cell 15:813-28
Sharma, Ved P; DesMarais, Vera; Sumners, Colin et al. (2008) Immunostaining evidence for PI(4,5)P2 localization at the leading edge of chemoattractant-stimulated HL-60 cells. J Leukoc Biol 84:440-7
Frantz, Christian; Barreiro, Gabriela; Dominguez, Laura et al. (2008) Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding. J Cell Biol 183:865-79
Sarmiento, Corina; Wang, Weigang; Dovas, Athanassios et al. (2008) WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells. J Cell Biol 180:1245-60

Showing the most recent 10 out of 36 publications