membrane traffic, exocytosis, cell polarity, morphogenesis, cytoskeleton, cancer metastasis
Membrane traffic, exocytosis, exocyst, cell polarity, actin cytoskeleton, cell growth, morphogenesis, small GTPases, Rab, Rho, cancer, metastasis, Polycycstic Kidney Diseases
Exocytosis is a basic membrane traffic event mediated by transport, docking, and fusion of secretory vesicles carrying proteins and lipids to the plasma membrane. Through exocytosis, hormones and neurotransmitters can be released. Also through exocytosis, membrane proteins and lipids can be incorporated into specific domains of plasma membrane for cell surface expansion, cell growth, morphogenesis, and cell migration. Our research aims to address two fundamental questions in cell and developmental biology: (1) what is the molecular basis for exocytosis; and (2) how do the secretory machinery functions in concert with cytoskeleton and small-GTP-binding proteins during cell polarization, morphogenesis, and cancer cell metastasis.
Our research focuses on an evolutionarily conserved multi-protein complex, named the exocyst. The exocyst consists of eight components: Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84. All play essential roles in secretory vesicle targeting and docking at the plasma membrane for exocytosis. The exocyst is specifically localized to sites of active exocytosis and polarized cell growth. In budding yeast, the exocyst proteins are localized to the tip of the budding daughter cells (bud tip), a region of active exocytosis and cell surface expansion. In developing neurons, the exocyst is localized to the tips of growing neurites. In epithelial cells, the exocyst is concentrated near the adherens junction, a region of active basolateral membrane addition. The exocyst complex is a downstream effector of small GTPases including Rab, Rho, and Ral. Through interacting with this multiprotein exocyst complex, these small G-proteins can spatially and kinetically regulate exocytosis and membrane morphology. Besides the small GTPases, the exocyst also interact with cytoskeleton and other signaling molecules in the cell. The assembly of the exocyst complex therefore integrates various sources of cellular information to ensure the accuracy of exocytosis and morphogenesis.
Our goal is to understand how this important secretory machinery works using a combination of biochemistry, molecular biology, genetics, and cell biology approaches. Furthermore, through studying the exocyst complex, we aim to learn how multiple cellular machines are coordinated to carry out important biological functions such as morphogenesis and cell migration. We study the exocyst in both yeast and mammalian cells: the budding yeast Saccharomyces cerevisiae grows asymmetrically by "budding", a seemingly simple process that requires sophisticated mechanisms that coordinate membrane traffic, cell polarity and cell cycle progression. This property, in combination with its facile genetics and well-characterized genomics, makes the budding yeast a powerful model system for our research. We also study the exocyst in mammalian cells, in which we investigate the role of the exocyst in morphogenesis and cell migration. Taking advantage of these two different eukaryotic systems in parallel, we wish to elucidate the basic mechanisms of exocytosis and cell morphogenesis and their involvement in cancer, polycystic kidney diseases, and diabetes.
Zhao Yuting, Guo Wei: Sec-ure nanotubes with RalA and exocyst. Nature cell biology 11(12): 1396-7, Dec 2009.
Liu Jianglan, Yue Peng, Artym Vira V, Mueller Susette C, Guo Wei: The role of the exocyst in matrix metalloproteinase secretion and actin dynamics during tumor cell invadopodia formation. Molecular biology of the cell 20(16): 3763-71, Aug 2009.
He Bing, Guo Wei: The exocyst complex in polarized exocytosis. Current opinion in cell biology 21(4): 537-42, Aug 2009.
Orlando Kelly, Zhang Jian, Zhang Xiaoyu, Yue Peng, Chiang Teresa, Bi Erfei, Guo Wei: Regulation of Gic2 localization and function by phosphatidylinositol 4,5-bisphosphate during the establishment of cell polarity in budding yeast. The Journal of biological chemistry 283(21): 14205-12, May 2008.
Zhang Xiaoyu, Orlando Kelly, He Bing, Xi Fengong, Zhang Jian, Zajac Allison, Guo Wei: Membrane association and functional regulation of Sec3 by phospholipids and Cdc42. The Journal of cell biology 180(1): 145-58, Jan 2008.
Liu Jianglan, Zuo Xiaofeng, Yue Peng, Guo Wei: Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells. Molecular biology of the cell 18(11): 4483-92, Nov 2007.
He Bing, Xi Fengong, Zhang Xiaoyu, Zhang Jian, Guo Wei: Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane. The EMBO journal 26(18): 4053-65, Sep 2007.
Zuo Xiaofeng, Zhang Jian, Zhang Ying, Hsu Shu-Chan, Zhou Daoguo, Guo Wei: Exo70 interacts with the Arp2/3 complex and regulates cell migration. Nature cell biology 8(12): 1383-8, Dec 2006.
He Bing, Xi Fengong, Zhang Jian, TerBush Daniel, Zhang Xiaoyu, Guo Wei: Exo70p mediates the secretion of specific exocytic vesicles at early stages of the cell cycle for polarized cell growth. The Journal of cell biology 176(6): 771-7, Mar 2007.
EauClaire S.F. and Guo, W.: Conservation and specialization: the role of the exocyst in neuronal exocytosis.
Neuron 37: 369-374, 2003.
Novick, P. and Guo, W.: Ras family therapy: Rab, Rho and Ral talk to the exocyst.
Trends in Cell Biol. 12(6): 247-249, 2002.
Guo, W., Tamanoi, F., and Novick, P.: Spatial regulation of the exocyst complex by Rho1 GTPase. NATURE-Cell Biology 3(4): 353-360, 2001.
Zajac, A., Sun, X., Zhang, J. and Guo, W.: Cyclical Regulation of the Exocyst and Cell Polarity Determinants for Polarized Growth. Mol. Biol. Cell 16(3): 1500-1512, 2005.
Zhang Xiaoyu, Wang Puyue, Gangar Akanksha, Zhang Jian, Brennwald Patrick, TerBush Daniel, Guo Wei: Lethal giant larvae proteins interact with the exocyst complex and are involved in polarized exocytosis. The Journal of cell biology 170(2): 273-83, Jul 2005.
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Last updated: 01/05/2010
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