Dynamics of Secretory Membrane Trafficking and Sorting

Lippincott-Schwartz, Jennifer A.

Abstract

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.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
• Type: Intramural Research (Z01)
• Project #: 1Z01HD001609-10
• Application #: 6834298
• Study Section: (CBMB)
• Support Year: 10
• Fiscal Year: 2003

Institution

• Name: U.S. National Inst/Child Hlth/Human Dev
• Country: United States

Publications

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

Altan-Bonnet, Nihal; Sougrat, Rachid; Liu, Wei et al. (2006) Golgi inheritance in mammalian cells is mediated through endoplasmic reticulum export activities. Mol Biol Cell 17:990-1005

Rey, Osvaldo; Papazyan, Romeo; Waldron, Richard T et al. (2006) The nuclear import of protein kinase D3 requires its catalytic activity. J Biol Chem 281:5149-57