Wei Guo, Ph.D.
Associate Professor, Dept of Biology

Cell Biology and Physiology Program

Address

304E Lynch Laboratories
433 S. University Ave.
Philadelphia, PA 19104-6018

Office tel.: 215 898-9384
Lab tel.: 215 573-7255
Fax: 215 898-8780
E-mail: guowei@sas.upenn.edu

Research Interests

• membrane traffic, exocytosis, cell polarity, morphogenesis, cytoskeleton, cancer metastasis

Key words: Membrane traffic, exocytosis, exocyst, cell polarity, actin cytoskeleton, cell growth, morphogenesis, small GTPases, Rab, Rho, cancer, metastasis, Polycycstic Kidney Diseases

Description of Research

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.

Selected Publications

Zhang, X., Orlando, K., He, B., Xi, F., Zhang, J., Zajac, A., and Guo, W. Membrane association and functional regulation of Sec3 by phospholipids and Cdc42. J. Cell Biol. (2008). 180(1): 145-158.

Liu, J., Zuo, X., Yue, P., and Guo, W. (2007) Phosphatidylinositol 4, 5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells. Mol. Biol. Cell. 18(11):4483-4492.

He, B., Xi, F., Zhang, X., Zhang, J., and Guo, W. (2007) Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane. EMBO J. 26, 4053-4065.

He, B., Xi, F., Zhang, J., TerBush D., Zhang, X., and Guo, W. (2007) Exo70 mediates the secretion of specific exocytic vesicles at early stages of cell cycle for polarized cell growth. J. Cell Biol. 176(6):771-777.

Zuo, X., Zhang, J., Zhang, Y., Hsu, S., Zhou, D., and Guo, W. (2006) Exo70 interacts with the Arp2/3 complex and regulates cell migration. Nature-Cell Biology 8(12):1383-1388.

Zhang, X., Wang, P., Gangar, A., Zhang, J., Brennwald, P., TerBush, D., and Guo, W. (2005) Lethal giant larvae proteins interact with the exocyst complex and is involved in polarized exocytosis J. Cell Biol. 170(2):273-83.

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