Faculty and Research
Faculty by Name
Hsiao-Ping Moore
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Hsiao-Ping Moore
Research Interests
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Our laboratory is interested in molecular mechanisms that control the intracellular localization of proteins in mammalian cells. Specifically, we are studying how secretory and membrane proteins are routed, sorted, and targeted to specific organelles in neuronal and endocrine cells. Using biochemical, molecular biological, and morphological approaches, we hope to identify the signals that encode address information of proteins, and to understand how such information is decoded by cellular machinery.
Current Projects
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The effectiveness of cell-cell communication in higher eucaryotes depends critically on the precise intracellular location of neurotransmitters and hormones within neuroendocrine cells. Chemical messengers are packaged in unique membrane-bound secretory organelles whose exocytosis is triggered by external stimuli. The exact mechanism by which secretory products are targeted from their site of synthesis to the secretory granules is not fully understood. Moreover, the molecular events underlying assembly of these secretory granules are poorly defined. Our research projects are divided into the following areas: (1) molecular sorting of proteins in the secretory apparatus; (2) control of propeptide processing; and (3) formation and maturation of secretory vesicles.
Sorting of secretory proteins. In differentiated tissues specialized in secretory function secretory products are segregated into distinct classes secretory vesicles. In addition to the regulated pathway for secretion of peptide hormones, the cell has a second, constitutive, pathway for the export of newly synthesized plasma membrane proteins and components of the extracellular matrix. Using electron microscopy, we have identified the compartment at which hormones are segregated from other secretory products to be the trans Golgi network. The nature and specificity of this sorting event were studied by DNA transfection and in vitro mutagenesis techniques. The results of these studies suggest that constitutive proteins exit the trans Golgi by a bulk-flow process, whereas entry into the regulated pathway requires special structural features for proper sorting.
Control of prohormone processing. Most bioactive peptides are synthesized as larger precursors which become activated by proteolytic processing in specific secretory compartments. Acidification of the secretory pathway plays a key role in controlling compartment-specific propeptide processing. How individual compartment maintains its unique pH value is unknown. We have developed a novel avidin-targeted fluorescence method tostudy pH regulation along the secretory pathway. Our results indicate that individual compartment controls its acidity by balancing proton pump rates and proton leak rates. Gradual acidification along this path thus requires sorting of both proton pumps and proton leak channels
Formation and maturation of exocytotic vesicles. In order to dissect the processes of vesicle formation, we have developed a variety of in vitro systems that reconstitute transport between the trans-Golgi and the cell surface. Using these systems we are investigating the role of cytoplasmic coat proteins in the sorting and assembly of regulated secretory granules. In addition, we are studying other regulatory components involved in the production of constitutive and regulated exocytic vesicles. Proper maturation of secretory carriers also involves membrane remodeling and sorting of SNARE proteins. These post-Golgi vesicle trafficking events are being studied at a molecular level.
Selected Publications
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Biosynthesis and secretion of pituitary hormones: Dynamics and Regulation. [H.-P. H. Moore, J. M. Andresen, B. A. Eaton, M. Grabe, M. Haugwitz, M. M. Wu & T. E. Machen (2002) Arch. Physiol. and Biochem. 110:16-25]
Biogenesis of processing-competent secretory organelles in vitro. [J. M. Andresen & H.-P. H. Moore (2001) Biochemistry, 40:13020-13030]
Mechanisms of pH regulation in the regulated secretory pathway. [M. M. Wu, M. Grabe, S. Adams, R. Y. Tsien, H.-P. H. Moore, T. E. Machen (2001) J. Biol. Chem. 276:33027-33035]
Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells. [G. Chandy, M. Grabe, H.-P. H. Moore & T. E. Machen (2001) Am. J. of Physiology: Cell Physiology 281: C908-C921]
Studying organelle physiology using targeted avidin and fluorescein-biotin. [M. M. Wu, J. Llopis, S. Adams, J. M. McCaffery, K. Teter, M. S. Kulomaa, T. Machen, H.-P. H. Moore, and R. Y. Tsien (2000) Methods in Enzymology, 327:546-64]
Biogenesis of regulated exocytotic carriers in neuroendocrine cells. [B. A. Eaton, M. Haugwitz, D. Lau & H.-P. H. Moore (2000) J. Neuroscience, 20, 7334-7344]
Organelle pH studies using targeted avidin and fluorescein-biotin. [M. M. Wu, J. Llopis, S. Adams, M. McCaffery, M. S. Kulomaa, T. Machen, H.-P. H. Moore, and R. Y. Tsien (2000) Chemistry and Biology 7, 197-209]
Focal exocytosis of VAMP3-containing vesicles at sites of phagosome formation. [L. Bajno, X.-R. Peng, A. D. Schreiber, H.-P. H. Moore, W. S. Trimble, and S. Grinstein (2000) J. Cell Biology 149, 697-705]
Last Updated 2004-09-07