The Section on Organelle Biology investigates the global principles underlying secretory membrane trafficking, sorting and compartmentalization within eukaryotic cells. Live cell imaging of green fluorescent protein (GFP) fusion proteins in combination with photobleaching and photoactivation techniques are being used to investigate the subcellular localization, mobility, transport routes and binding interactions of a variety of proteins with important roles in the organization and regulation of membrane traffic and compartmentalization. Quantitative measurements of these protein characteristics are used in kinetic modeling and simulation experiments in order to test mechanistic hypotheses related to protein and organelle dynamics. Among the topics currently under study include: growth and maintenance of endoplasmic reticulum (ER) and Golgi morphology in mammalian cells and in developing Drosophila embryos; the mechanism(s) of secretory protein transport into and out of the Golgi apparatus; membrane binding/dissociation kinetics of trafficking machinery and its regulation; the generation and maintenance of cell polarity; and, organelle breakdown and reassembly during mitosis. We have also recently developed a photoactivatable GFP, whose mechanism of photoactivation is currently being investigated.

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Budget End
Support Year
11
Fiscal Year
2004
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Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
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Country
United States
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Mavrakis, Manos; Rikhy, Richa; Lippincott-Schwartz, Jennifer (2009) Cells within a cell: Insights into cellular architecture and polarization from the organization of the early fly embryo. Commun Integr Biol 2:313-4
Hailey, Dale W; Lippincott-Schwartz, Jennifer (2009) Using photoactivatable proteins to monitor autophagosome lifetime. Methods Enzymol 452:25-45
Gillette, Jennifer M; Lippincott-Schwartz, Jennifer (2009) Hematopoietic progenitor cells regulate their niche microenvironment through a novel mechanism of cell-cell communication. Commun Integr Biol 2:305-7
Shtengel, Gleb; Galbraith, James A; Galbraith, Catherine G et al. (2009) Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure. Proc Natl Acad Sci U S A 106:3125-30
Patterson, George H; Hirschberg, Koret; Polishchuk, Roman S et al. (2008) Transport through the Golgi apparatus by rapid partitioning within a two-phase membrane system. Cell 133:1055-67
Belov, George A; Altan-Bonnet, Nihal; Kovtunovych, Gennadiy et al. (2007) Hijacking components of the cellular secretory pathway for replication of poliovirus RNA. J Virol 81:558-67
Mavrakis, Manos; Lippincott-Schwartz, Jennifer; Stratakis, Constantine A et al. (2007) mTOR kinase and the regulatory subunit of protein kinase A (PRKAR1A) spatially and functionally interact during autophagosome maturation. Autophagy 3:151-3
Wakabayashi, Yoshiyuki; Chua, Jennifer; Larkin, Janet M et al. (2007) Four-dimensional imaging of filter-grown polarized epithelial cells. Histochem Cell Biol 127:463-72
Frescas, David; Mavrakis, Manos; Lorenz, Holger et al. (2006) The secretory membrane system in the Drosophila syncytial blastoderm embryo exists as functionally compartmentalized units around individual nuclei. J Cell Biol 173:219-30
Lorenz, Holger; Hailey, Dale W; Lippincott-Schwartz, Jennifer (2006) Fluorescence protease protection of GFP chimeras to reveal protein topology and subcellular localization. Nat Methods 3:205-10

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